Thrombosis inhibiting graft

ABSTRACT

A medical method that is adapted for introducing the medical device into the vascular system of a body which is designed to inhibit or prevent thrombosis after the insertion of the medical device.

The present invention claims priority on U.S. Provisional ApplicationSer. No. 60/629,470 filed Nov. 19, 2004 and 60/658,411 filed Mar. 3,2005, which are incorporated herein by reference.

The present invention is also a continuation in part of U.S. applicationSer. No. 10/810,356 filed Mar. 26, 2004, which in turn is a continuationof U.S. application Ser. No. 10/039,816 filed on Oct. 26, 2001, which inturn is a continuation-in-part of U.S. patent application Ser. No.09/771,073 filed Jan. 29, 2001, which in turn is a continuation-in-partof U.S. patent application Ser. No. 09/363,052 filed Jul. 29, 1999, nowU.S. Pat. No. 6,206,916, which in turn claims priority on U.S.Provisional Patent Application Ser. No. 60/094,250 filed Jul. 27, 1998,which are incorporated herein by reference.

The present invention is also a continuation in part of U.S. applicationSer. No. 10/209,591 filed Jul. 30, 2002, which in turn is acontinuation-in-part of U.S. patent application Ser. No. 10/039,816filed Oct. 26, 2001, which in turn is a continuation-in-part of U.S.patent application Ser. No. 09/771,073 filed Jan. 29, 2001, which inturn is a continuation-in-part of U.S. patent application Ser. No.09/363,052 filed Jul. 29, 1999, now U.S. Pat. No. 6,206,916, which inturn claims priority on U.S. Provisional Patent Application Ser. No.60/094,250 filed Jul. 27, 1998, which are incorporated herein byreference.

The invention relates generally to medical devices, and particularly toan implant for use within a body, and more particularly to an expandablegraft which is useful in repairing various types of body passageways,and even more particularly to an expandable graft which is useful inrepairing blood vessels narrowed or occluded by disease.

BACKGROUND OF THE INVENTION

Medical treatment of various illnesses or diseases commonly includes theuse of one or more medical devices. Two types of medical devices thatare commonly used to repair various types of body passageways are anexpandable graft or stent, or a surgical graft. These devices have beenimplanted in various areas of the mammalian anatomy.

Old age, dietary habits and primary genetics can also lead to a commondisease, atherosclerosis. Atherosclerotic plaques and blockages consistof lipids, fibroblasts and fibrin that proliferate and cause obstructionof a vessel. As the obstruction grows, the blood flow diminishes andreaches a level that is insufficient to meet the biological needs of oneor more organs. The end result is defined as ischemia.

One purpose of a stent is to open a blocked or partially blocked bodypassageway. When a stent is used in a blood vessel, the stent is used toopen the occluded vessel to achieve improved blood flow which isnecessary to provide for the anatomical function of an organ. Theprocedure of opening a blocked or partially blocked body passagewaycommonly includes the use of one or more stents in combination withother medical devices such as, but not limited to, an introducer sheath,a guiding catheter, a guide wire, an angioplasty balloon, etc.

During the insertion of the stent, some disruption of the native bodypassageway can occur. This disruption to the body passageway can start acascade of biological occurrences that can hinder the function of theimplanted stent. When a stent is inserted into a blood vessel, a)platelets can be activated, b) smooth muscle cells can migrate and/or c)endothelial cells, which protect the vessel, can be disrupted thusleading to the cascade of clot formation. Clot formation can lead to thefailure of the stent. The accumulation of platelets about the implantedstent is known as thrombosis.

Another medical procedure that is utilized frequently involves bypass(heart surgery), or peripheral (non-cardiac) grafting. This medicalprocedure entails using a surgical graft constructed of an artificialmaterial that replaces or by-passes the diseased portion of the vessel.This procedure is accomplished by ligating the diseased portion of thevessel, temporarily stopping blood flow, and physically sewing in thesurgical with a suture. The failure of the medical procedure commonlyoccurs at the suture (anastomoses) site. When the surgical graft isconnected to a blood vessel, a) platelets can be activated, b) smoothmuscle cells can migrate and/or c) endothelial cells, which protect thevessel, can be disrupted thus leading to the cascade of clot formation.The clot formation can lead to the failure of the surgical graft. Theaccumulation of platelets about the sutured regions is also known asthrombosis. This failure can then lead to repeat procedures, amputationand/or other medical complications.

During and after a medical procedure, the patient is commonly placed onaggressive anti-platelet and/or anti-coagulation therapy. A majorconcern and side effect of such treatment is an increased incidence ofbleeding complications. These bleeding complications can make the mostroutine procedure such as getting your teeth cleaned prohibited.

Many other types of diseases are treatable with stents, catheters,surgical grafts, and/or other devices inserted into vessels or otherlocations in the body. In addition, various types of orthopedic devicescan be used to treat various diseased and/or damaged areas of a body.One desirable technique would be to deliver one or more biologicalagents directly to the site that has been treated and/or at the site ofpotential failure once a medical device has been inserted in thetreatment site. In one non-limiting example, it would be desirable tohave a medical device and/or a medical method or technique that can beused to deliver an anti-platelet and/or other medication to the regionof a body passageway which has been treated by a stent or by anotherinterventional technique. In another and/or alternative non-limitingexample, it would be desirable to have a medical device that coulddeliver one or more biological agents over the short term (e.g, seconds,minutes, hours, days) with a potential burst effect of the one or morebiological agents, and/or the long term (e.g. days, weeks, months,years) after the initial implantation of the medical device. In stillanother and/or alternative non-limiting example, it would be desirableto provide control over the delivery rate of one or more biologicalagents from the medical device, thus limiting or eliminating thesystemic effects of taking a drug (e.g, orally, intravenously, etc.)over extended periods of time.

In view of the present state of medical device technology, there is aneed and demand for a medical device that can be inserted into atreatment site and which has improved procedural success rates andinhibits or prevents the occurrence of thrombosis after the medicaldevice has been inserted into the treatment area result in theelimination of the need for or the reduction in the need for aggressiveanti-platelet and/or anti-coagulation therapy after insertion of themedical device.

SUMMARY OF THE INVENTION

The previously mentioned short-comings of prior art medical devices areaddressed by the novel medical device of the present invention. Themedical device of the present invention can be designed to be insertedinto a treatment site such that the medical device has improvedprocedural success rates and inhibits or prevents the occurrence ofthrombosis after the medical device has been inserted into the treatmentarea. The improved procedural success rate and the inhibition orprevention of the occurrence of thrombosis by the medical device of thepresent invention can be achievable without the need for or with asignificant reduction in need for aggressive anti-platelet and/oranti-coagulation therapy after insertion of the medical device in thetreatment area. The improved medical procedure of the present inventioncan be at least partially obtained by the use of a medical devicethat 1) is formed of one or more materials that enhances the physicalproperties of the medical device, and/or 2) includes one or morebiological agents (e.g., anti-platelet medication, etc.) that can becontrollably and/or uncontrollably delivered at, adjacent to and/or intoa treatment site by the medical device. The medical device in accordancewith the present invention can be in the form of many different devicessuch as, but not limited to, stents, grafts, surgical grafts (e.g.,vascular grafts, etc.), valves, orthopedic implants, sheaths, guidewires, balloon catheters, hypotubes, catheters (e.g., electrophysiologycatheters, guide catheter, stent catheter, etc.), cutting devices, PFO(patent foramen ovale) device, sutures, staples, bandages, wraps,biological glue, etc. In one non-limiting embodiment, the medical deviceis directed for use in a body passageway. As defined herein, the term“body passageway” is defined to be any passageway or cavity in a livingorganism (e.g., bile duct, bronchiole tubes, nasal cavity, bloodvessels, heart, esophagus, trachea, stomach, fallopian tube, uterus,ureter, urethra, the intestines, lymphatic vessels, nasal passageways,eustachian tube, acoustic meatus, etc.). The techniques employed todeliver the medical device to a treatment area include, but are notlimited to, angioplasty, vascular anastomoses, transplantation,implantation, subcutaneous introduction, minimally invasive surgicalprocedures, injection, topical applications, bolus administration,infusion, interventional procedures, and any combinations thereof. Forvascular applications, the term “body passageway” primarily refers toblood vessels and chambers in the heart. When the medical device is inthe form of a stent, the stent can be an expandable stent that isexpandable by a balloon and/or other means. The stent can have manyshapes and forms. Such shapes can include, but are not limited to,stents disclosed in U.S. Pat. Nos. 6,206,916 and 6,436,133; and all theprior art cited in these patents. These various designs andconfigurations of stents in such patents are incorporated herein byreference.

In one non-limiting aspect of the present invention, the medical devicehas one or more features that at least partially result in theinhibition or prevention of thrombosis after the medical device has beenimplanted in a treatment area. These features include, but are notlimited to, 1) the shape and/or profile of the medical device, 2) theone or more materials that are used to at least partially form themedical device, and/or 3) the one or more biological agents that are atleast partially coated on, contained therein and/or included in themedical device. As a result, the need or use of body-wide standardaggressive anti-platelet and/or anti-coagulation therapy for extendedperiods of time to inhibit or prevent the occurrence of thrombosis isnot required in conjunction with the medical device of the presentinvention. In the past, the use of body-wide therapy was used by thepatient long after the patient left the hospital or other type ofmedical facility. This body-wide therapy could last days, weeks, monthsor sometimes over a year after surgery. The medical device of thepresent invention can be applied or inserted into a treatment areaand 1) merely require reduced use of body wide therapy after applicationor insertion of the medical device, or 2) does not require use of bodywide therapy after application or insertion of the medical device. Assuch, the medical device of the present invention can be designed to beinserted in a treatment area without any temporary use and/or withoutextended use of body wide aggressive anti-platelet and/oranti-coagulation therapy after the medical device has been inserted inthe treatment area. This method of treating a treatment area with amedical device while inhibiting or preventing the occurrence ofthrombosis at or near the treatment area is a significant improvementover past treatment procedures. In one non-limiting example, nobody-wide therapy is needed after the insertion of the medical deviceinto a patient. In another and/or alternative non-limiting example,short term use of body-wide therapy is needed or used after theinsertion of the medical device into a patient. Such short term use canbe terminated after the release of the patient from the hospital orother type of medical facility, or one to two days or weeks after therelease of the patient from the hospital or other type of medicalfacility; however, it will be appreciated that other time periods ofbody-wide therapy can be used. As a result of the use of the medicaldevice of the present invention, the use of body-wide therapy after amedical procedure involving the insertion of a medical device into atreatment area can be significantly reduced or eliminated.

In another and/or alternative non-limiting aspect of the presentinvention, the medical device can include, contain and/or be coated withone or more biological agents that inhibits or prevents thrombosisduring and/or after the medical device has been inserted into atreatment area. In one non-limiting embodiment, the one or morebiological agents that can be include with, contained in and/or becoated on the medical device include, but are not limited to, ananti-platelet compound and/or anticoagulant compound such as, but notlimited to, warfarin (Coumadin), warfarin derivatives, aspirin, aspirinderivatives, clopidogrel, clopidogrel derivatives, ticlopadine,ticlopadine derivatives, hirdun, hirdun derivatives, dipyridamole,dipyridamole derivatives, trapidil, trapidil derivatives, taxol, taxolderivatives, cytochalasin, cytochalasin derivatives, paclitaxel,paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF, GM-CSFderivatives, heparin, heparin derivatives, low molecular weight heparin,low molecular weight heparin derivatives, or combinations thereof. Onespecific non-limiting example of an anti-thrombotic inhibitor that canbe include with, contained in and/or be coated on the medical deviceincludes 1) huridin and/or derivatives, and/or 2) alagors (e.g.,bivalirudin, etc.) and/or derivatives. As can be appreciated, one ormore other anti-thrombotic biological agents can be used with themedical device.

In yet another and/or alternative non-limiting aspect of the presentinvention, the medical device can include, contain and/or be coated withone or more biological agents that facilitate in the success of themedical device and/or treated area. As indicated above, the medicaldevice can include, contain and/or be coated with one or more biologicalagents that inhibit or prevent thrombosis during and/or after themedical device is inserted into a treatment area. In addition oralternatively, the medical device can include, contain and/or be coatedwith one or more biological agents that can be used in conjunction withthe one or more biological agents that inhibit or prevent thrombosisthat are included in, contained in and/or coated in the medical device.As such, the medical device, when it includes, contains and/or is coatedwith one or more biological agents, can include one or more biologicalagents that inhibit or prevent thrombosis and/or perform one or moreother function(s). The term “biological agent” includes, but is notlimited to, a substance, drug or otherwise formulated and/or designed toprevent, inhibit and/or treat one or more biological problems, and/or topromote the healing in a treated area. Non-limiting examples ofbiological problems that can be addressed by one or more biologicalagents include, but are not limited to, viral, fungus and/or bacteriainfection; vascular diseases and/or disorders; digestive diseases and/ordisorders; reproductive diseases and/or disorders; lymphatic diseasesand/or disorders; cancer; implant rejection; pain; nausea; swelling;arthritis; bone diseases and/or disorders; organ failure; immunitydiseases and/or disorders; cholesterol problems; blood diseases and/ordisorders; lung diseases and/or disorders; heart diseases and/ordisorders; brain diseases and/or disorders; neuralgia diseases and/ordisorders; kidney diseases and/or disorders; ulcers; liver diseasesand/or disorders; intestinal diseases and/or disorders; gallbladderdiseases and/or disorders; pancreatic diseases and/or disorders;psychological disorders; respiratory diseases and/or disorders; glanddiseases and/or disorders; skin diseases and/or disorders; hearingdiseases and/or disorders; oral diseases and/or disorders; nasaldiseases and/or disorders; eye diseases and/or disorders; fatigue;genetic diseases and/or disorders; burns; scarring and/or scars; trauma;weight diseases and/or disorders; addiction diseases and/or disorders;hair loss; cramps; muscle spasms; tissue repair; and/or the like.Non-limiting examples of biological agents that can be used include, butare not limited to, 5-Fluorouracil and/or derivatives thereof;5-Phenylmethimazole and/or derivatives thereof; ACE inhibitors and/orderivatives thereof; acenocoumarol and/or derivatives thereof; acyclovirand/or derivatives thereof; actilyse and/or derivatives thereof;adrenocorticotropic hormone and/or derivatives thereof; adriamycinand/or derivatives thereof; agents that modulate intracellular Ca₂₊transport such as L-type (e.g., diltiazem, nifedipine, verapamil, etc.)or T-type Ca₂₊ channel blockers (e.g., amiloride, etc.);alpha-adrenergic blocking agents and/or derivatives thereof; alteplaseand/or derivatives thereof; amino glycosides and/or derivatives thereof(e.g., gentamycin, tobramycin, etc.); angiopeptin and/or derivativesthereof; angiostatic steroid and/or derivatives thereof; angiotensin IIreceptor antagonists and/or derivatives thereof; anistreplase and/orderivatives thereof; antagonists of vascular epithelial growth factorand/or derivatives thereof; anti-biotics; anti-coagulant compoundsand/or derivatives thereof; anti-fibrosis compounds and/or derivativesthereof; anti-fungal compounds and/or derivatives thereof;anti-inflammatory compounds and/or derivatives thereof; Anti-InvasiveFactor and/or derivatives thereof; anti-metabolite compounds and/orderivatives thereof (e.g., staurosporin, trichothecenes, and modifieddiphtheria and ricin toxins, Pseudomonas exotoxin, etc.); anti-matrixcompounds and/or derivatives thereof (e.g., colchicine, tamoxifen,etc.); anti-microbial agents and/or derivatives thereof; anti-migratoryagents and/or derivatives thereof (e.g., caffeic acid derivatives,nilvadipine, etc.); anti-mitotic compounds and/or derivatives thereof;anti-neoplastic compounds and/or derivatives thereof; anti-oxidantsand/or derivatives thereof; anti-platelet compounds and/or derivativesthereof; anti-proliferative and/or derivatives thereof;anti-thrombogenic agents and/or derivatives thereof; argatroban and/orderivatives thereof; ap-1 inhibitors and/or derivatives thereof (e.g.,for tyrosine kinase, protein kinase C, myosin light chain kinase,Ca₂₊/calmodulin kinase II, casein kinase II, etc.); aspirin and/orderivatives thereof; azathioprine and/or derivatives thereof;β-Estradiol and/or derivatives thereof; β-1-anticollagenase and/orderivatives thereof; calcium channel blockers and/or derivativesthereof; calmodulin antagonists and/or derivatives thereof (e.g., H₇,etc.); CAPTOPRIL and/or derivatives thereof; cartilage-derived inhibitorand/or derivatives thereof; ChIMP-3 and/or derivatives thereof;cephalosporin and/or derivatives thereof (e.g., cefadroxil, cefazolin,cefaclor, etc.); chloroquine and/or derivatives thereof;chemotherapeutic compounds and/or derivatives thereof (e.g.,5-fluorouracil, vincristine, vinblastine, cisplatin, doxyrubicin,adriamycin, tamocifen, etc.); chymostatin and/or derivatives thereof;CILAZAPRIL and/or derivatives thereof; clopidigrel and/or derivativesthereof; clotrimazole and/or derivatives thereof; colchicine and/orderivatives thereof; cortisone and/or derivatives thereof; coumadinand/or derivatives thereof; curacin-A and/or derivatives thereof;cyclosporine and/or derivatives thereof; cytochalasin and/or derivativesthereof; (e.g., cytochalasin A, cytochalasin B, cytochalasin C,cytochalasin D, cytochalasin E, cytochalasin F, cytochalasin G,cytochalasin H, cytochalasin J, cytochalasin K, cytochalasin L,cytochalasin M, cytochalasin N, cytochalasin O, cytochalasin P,cytochalasin Q, cytochalasin R, cytochalasin S, chaetoglobosin A,chaetoglobosin B, chaetoglobosin C, chaetoglobosin D, chaetoglobosin E,chaetoglobosin F, chaetoglobosin G, chaetoglobosin J, chaetoglobosin K,deoxaphomin, proxiphomin, protophomin, zygosporin D, zygosporin E,zygosporin F, zygosporin G, aspochalasin B, aspochalasin C, aspochalasinD, etc.); cytokines and/or derivatives thereof; desirudin and/orderivatives thereof; dexamethazone and/or derivatives thereof;dipyridamole and/or derivatives thereof; eminase and/or derivativesthereof; endothelin and/or derivatives thereof; endothelial growthfactor and/or derivatives thereof; epidermal growth factor and/orderivatives thereof; epothilone and/or derivatives thereof; estramustineand/or derivatives thereof; estrogen and/or derivatives thereof;fenoprofen and/or derivatives thereof; fluorouracil and/or derivativesthereof; flucytosine and/or derivatives thereof; forskolin and/orderivatives thereof; ganciclovir and/or derivatives thereof;glucocorticoids and/or derivatives thereof (e.g., dexamethasone,betamethasone, etc.); glycoprotein IIb/IIIa platelet membrane receptorantibody and/or derivatives thereof; GM-CSF and/or derivatives thereof;griseofulvin and/or derivatives thereof; growth factors and/orderivatives thereof (e.g., VEGF; TGF; IGF; PDGF; FGF, etc.); growthhormone and/or derivatives thereof; heparin and/or derivatives thereof;hirudin and/or derivatives thereof; hyaluronate and/or derivativesthereof; hydrocortisone and/or derivatives thereof; ibuprofen and/orderivatives thereof; immunosuppressive agents and/or derivatives thereof(e.g., adrenocorticosteroids, cyclosporine, etc.); indomethacin and/orderivatives thereof; inhibitors of the sodium/calcium antiporter and/orderivatives thereof (e.g., amiloride, etc.); inhibitors of the IP₃receptor and/or derivatives thereof; inhibitors of the sodium/hydrogenantiporter and/or derivatives thereof (e.g., amiloride and derivativesthereof, etc.); insulin and/or derivatives thereof; Interferon alpha 2Macroglobulin and/or derivatives thereof; ketoconazole and/orderivatives thereof; Lepirudin and/or derivatives thereof; LISINOPRILand/or derivatives thereof; LOVASTATIN and/or derivatives thereof;marevan and/or derivatives thereof; mefloquine and/or derivativesthereof; metalloproteinase inhibitors and/or derivatives thereof;methotrexate and/or derivatives thereof; metronidazole and/orderivatives thereof; miconazole and/or derivatives thereof; monoclonalantibodies and/or derivatives thereof; mutamycin and/or derivativesthereof; naproxen and/or derivatives thereof; nitric oxide and/orderivatives thereof; nitroprusside and/or derivatives thereof; nucleicacid analogues and/or derivatives thereof (e.g., peptide nucleic acids,etc.); nystatin and/or derivatives thereof; oligonucleotides and/orderivatives thereof; paclitaxel and/or derivatives thereof; penicillinand/or derivatives thereof; pentamidine isethionate and/or derivativesthereof, phenindione and/or derivatives thereof; phenylbutazone and/orderivatives thereof; phosphodiesterase inhibitors and/or derivativesthereof; Plasminogen Activator Inhibitor-1 and/or derivatives thereof;Plasminogen Activator Inhibitor-2 and/or derivatives thereof; PlateletFactor 4 and/or derivatives thereof; platelet derived growth factorand/or derivatives thereof; plavix and/or derivatives thereof; POSTMI 75and/or derivatives thereof; prednisone and/or derivatives thereof;prednisolone and/or derivatives thereof; probucol and/or derivativesthereof; progesterone and/or derivatives thereof, prostacyclin and/orderivatives thereof; prostaglandin inhibitors and/or derivativesthereof; protamine and/or derivatives thereof; protease and/orderivatives thereof; protein kinase inhibitors and/or derivativesthereof (e.g., staurosporin, etc.); quinine and/or derivatives thereof;radioactive agents and/or derivatives thereof (e.g., Cu-64, Ca-67,Cs-131, Ga-68, Zr-89, Ku-97, Tc-99m, Rh-105, Pd-103, Pd-109, In-111,I-123, I-125, I-131, Re-186, Re-188, Au-198, Au-199, Pb-203, At-211,Pb-212, Bi-212, H₃P³²O₄, etc.); rapamycin and/or derivatives thereof;receptor antagonists for histamine and/or derivatives thereof; refludanand/or derivatives thereof; retinoic acids and/or derivatives thereof;revasc and/or derivatives thereof; rifamycin and/or derivatives thereof;sense or anti-sense oligonucleotides and/or derivatives thereof (e.g.,DNA, RNA, plasmid DNA, plasmid RNA, etc.); seramin and/or derivativesthereof; steroids; seramin and/or derivatives thereof; serotonin and/orderivatives thereof; serotonin blockers and/or derivatives thereof;streptokinase and/or derivatives thereof; sulfasalazine and/orderivatives thereof; sulfonamides and/or derivatives thereof (e.g.,sulfamethoxazole, etc.); sulphated chitin derivatives; SulphatedPolysaccharide Peptidoglycan Complex and/or derivatives thereof; T_(H1)and/or derivatives thereof (e.g., Interleukins-2, -12, and -15, gammainterferon, etc.); thioprotese inhibitors and/or derivatives thereof;taxol and/or derivatives thereof (e.g., taxotere, baccatin,10-deacetyltaxol, 7-xylosyl-10-deacetyltaxol, cephalomannine,10-deacetyl-7-epitaxol, 7 epitaxol, 10-deacetylbaccatin III,10-deacetylcephaolmannine, etc.); ticlid and/or derivatives thereof;ticlopidine and/or derivatives thereof; tick anti-coagulant peptideand/or derivatives thereof; thioprotese inhibitors and/or derivativesthereof; thyroid hormone and/or derivatives thereof; Tissue Inhibitor ofMetalloproteinase-1 and/or derivatives thereof; Tissue Inhibitor ofMetalloproteinase-2 and/or derivatives thereof; tissue plasmaactivators; TNF and/or derivatives thereof, tocopherol and/orderivatives thereof; toxins and/or derivatives thereof; tranilast and/orderivatives thereof; transforming growth factors alpha and beta and/orderivatives thereof; trapidil and/or derivatives thereof;triazolopyrimidine and/or derivatives thereof; vapiprost and/orderivatives thereof; vinblastine and/or derivatives thereof; vincristineand/or derivatives thereof; zidovudine and/or derivatives thereof. Ascan be appreciated, the biological agent can include one or morederivatives of the above listed compounds and/or other compounds. In onenon-limiting embodiment, the biological agent includes, but is notlimited to, trapidil, trapidil derivatives, taxol, taxol derivatives,cytochalasin, cytochalasin derivatives, paclitaxel, paclitaxelderivatives, rapamycin, rapamycin derivatives, 5-Phenylmethimazole,5-Phenylmethimazole derivatives, GM-CSF, GM-CSF derivatives, orcombinations thereof. The type and/or amount of biological agentincluded on, in and/or in conjunction with the medical device isgenerally selected for the treatment of one or more medical treatments.Typically the amount of biological agent included on, in and/or used inconjunction with the medical device is about 0.01-100 ug per mm²;however, other amounts can be used. The amount of two of more biologicalagents on, in and/or used in conjunction with the medical device can bethe same or different. In one non-limiting example, the medical devicecan be coated with and/or includes one or more biological agents suchas, but not limited to, trapidil and/or trapidil derivatives, taxol,taxol derivatives (e.g., taxotere, baccatin, 10-deacetyltaxol,7-xylosyl-10-deacetyltaxol, cephalomannine, 10-deacetyl-7-epitaxol, 7epitaxol, 10-deacetylbaccatin III, 10-deacetylcephaolmannine, etc.),cytochalasin, cytochalasin derivatives (e.g., cytochalasin A,cytochalasin B, cytochalasin C, cytochalasin D, cytochalasin E,cytochalasin F, cytochalasin G, cytochalasin H, cytochalasin J,cytochalasin K, cytochalasin L, cytochalasin M, cytochalasin N,cytochalasin O, cytochalasin P, cytochalasin Q, cytochalasin R,cytochalasin S, chaetoglobosin A, chaetoglobosin B, chaetoglobosin C,chaetoglobosin D, chaetoglobosin E, chaetoglobosin F, chaetoglobosin G,chaetoglobosin J, chaetoglobosin K, deoxaphomin, proxiphomin,protophomin, zygosporin D, zygosporin E, zygosporin F, zygosporin G,aspochalasin B, aspochalasin C, aspochalasin D, etc.), paclitaxel,paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF(granulo-cyte-macrophage colony-stimulating-factor), GM-CSF derivatives,or combinations thereof. In one non-limiting embodiment of theinvention, the medical device can be partially of fully coated with oneor more biological agents, impregnated with one or more biologicalagents to facilitate in the success of a particular medical procedure.The one or more biological agents can be coated on and/or impregnated inthe medical device by a variety of mechanisms such as, but not limitedto, spraying (e.g., atomizing spray techniques, etc.), dip coating, rollcoating, sonication, brushing, plasma deposition, depositing by vapordeposition. In another and/or alternative non-limiting embodiment of theinvention, the type and/or amount of biological agent included on, inand/or in conjunction with the medical device is generally selected forthe treatment of one or more medical treatments. Typically the amount ofbiological agent included on, in and/or used in conjunction with themedical device is about 0.01-100 ug per mm²; however, other amounts canbe used. The amount of two of more biological agents on, in and/or usedin conjunction with the medical device can be the same or different. Forinstance, one or more biological agents can be coated on, and/orincorporated in one or more portions of the medical device to providelocal and/or systemic delivery of one or more biological agents inand/or to a body passageway to a) inhibit or prevent thrombosis,in-stent restenosis, vascular narrowing and/or restenosis after themedical device has been inserted in and/or connected to a bodypassageway, b) at least partially passivate, remove and/or dissolvelipids, fibroblast, fibrin, etc. in a body passageway so as to at leastpartially remove such materials and/or to passivate such vulnerablematerials (e.g., vulnerable plaque, etc.) in the body passageway in theregion of the medical device and/or down stream of the medical device.As can be appreciated, the one or more biological agents can have manyother or additional uses. In another and/or alternative non-limitingexample, the medical device is coated with and/or includes one or morebiological agents such as, but not limited to, trapidil and/or trapidilderivatives, taxol, taxol derivatives, cytochalasin, cytochalasinderivatives, paclitaxel, paclitaxel derivatives, rapamycin, rapamycinderivatives, 5-Phenylmethimazole, 5-Phenylmethimazole derivatives,GM-CSF, GM-CSF derivatives, or combinations thereof. In still anotherand/or alternative non-limiting example, the medical device is coatedwith and/or includes one or more biological agents such as, but notlimited to trapidil, trapidil derivatives, taxol, taxol derivatives,cytochalasin, cytochalasin derivatives, paclitaxel, paclitaxelderivatives, rapamycin, rapamycin derivatives, 5-Phenylmethimazole,5-Phenylmethimazole derivatives, GM-CSF, GM-CSF derivatives, orcombinations thereof, and one or more additional biological agents, suchas, but not limited to, biological agents associated with thrombolytics,vasodilators, anti-hypertensive agents, anti-microbial or anti-biotic,anti-mitotic, anti-proliferative, anti-secretory agents, non-steroidalanti-inflammatory drugs, immunosuppressive agents, growth factors andgrowth factor antagonists, antitumor and/or chemotherapeutic agents,anti-polymerases, anti-viral agents, anti-body targeted therapy agents,hormones, anti-oxidants, biologic components, radio-therapeutic agents,radiopaque agents and/or radio-labeled agents. In addition to thesebiological agents, the medical device can be coated with and/or includeone or more biological agents that are capable of inhibiting orpreventing any adverse biological response by and/or to the medicaldevice that could possibly lead to device failure and/or an adversereaction by human or animal tissue. A wide range of biological agentsthus can be used.

In a further and/or alternative non-limiting aspect of the presentinvention, the one or more biological agents on and/or in the medicaldevice, when used on the medical device, can be released in a controlledmanner so the area in question to be treated is provided with thedesired dosage of biological agent over a sustained period of time. Ascan be appreciated, controlled release of one or more biological agentson the medical device is not always required and/or desirable. As such,one or more of the biological agents on and/or in the medical device canbe uncontrollably released from the medical device during and/or afterinsertion of the medical device in the treatment area. It can also beappreciated that one or more biological agents on and/or in the medicaldevice can be controllably released from the medical device and one ormore biological agents on and/or in the medical device can beuncontrollably released from the medical device. It can also beappreciated that one or more biological agents on and/or in one regionof the medical device can be controllably released from the medicaldevice and one or more biological agents on and/or in the medical devicecan be uncontrollably released from another region on the medicaldevice. As such, the medical device can be designed such that 1) all ofthe biological agent on and/or in the medical device is controllablyreleased, 2) some of the biological agent on and/or in the medicaldevice is controllably released and some of the biological agent on themedical device is non-controllably released, or 3) none of thebiological agent on and/or in the medical device is controllablyreleased. The medical device can also be designed such that the rate ofrelease of the one or more biological agents from the medical device isthe same or different. The medical device can also be designed such thatthe rate of release of the one or more biological agents from one ormore regions on the medical device is the same or different.Non-limiting arrangements that can be used to control the release of oneor more biological agent from the medical device include a) at leastpartially coat one or more biological agents with one or more polymers,b) at least partially incorporate and/or at least partially encapsulateone or more biological agents into and/or with one or more polymers,and/or c) insert one or more biological agents in pores, passageways,cavities, etc. in the medical device and at least partially coat orcover such pores, passageways, cavities, etc. with one or more polymers.As can be appreciated, other or additional arrangements can be used tocontrol the release of one or more biological agent from the medicaldevice. The one or more polymers used to at least partially control therelease of one or more biological agent from the medical device can beporous or non-porous. The one or more biological agents can be insertedinto and/or applied to one or more surface structures and/ormicro-structures on the medical device, and/or be used to at leastpartially form one or more surface structures and/or micro-structures onthe medical device. As such, the one or more biological agents on themedical device can be 1) coated on one or more surface regions of themedical device, 2) inserted and/or impregnated in one or more surfacestructures and/or micro-structures, etc. of the medical device, and/or3) form at least a portion or be included in at least a portion of thestructure of the medical device. When the one or more biological agentsare coated on the medical device, the one or more biological agentscan 1) be directly coated on one or more surfaces of the medical device,2) be mixed with one or more coating polymers or other coating materialsand then at least partially coated on one or more surfaces of themedical device, 3) be at least partially coated on the surface ofanother coating material that has been at least partially coated on themedical device, and/or 4) be at least partially encapsulated between a)a surface or region of the medical device and one or more other coatingmaterials and/or b) two or more other coating materials. As can beappreciated, many other coating arrangements can be additionally oralternatively used. When the one or more biological agents are insertedand/or impregnated in one or more internal structures, surfacestructures and/or micro-structures of the medical device, 1) one or moreother coating materials can be applied at least partially over the oneor more internal structures, surface structures and/or micro-structuresof the medical device, and/or 2) one or more polymers can be combinedwith one or more biological agents. As such, the one or more biologicalagents can be 1) embedded in the structure of the medical device; 2)positioned in one or more internal structures of the medical device; 3)encapsulated between two polymer coatings; 4) encapsulated between thebase structure and a polymer coating; 5) mixed in the base structure ofthe medical device that includes at least one polymer coating; or 6) oneor more combinations of 1, 2, 3, 4 and/or 5. In addition oralternatively, the one or more coating of the one or more polymers onthe medical device can include 1) one or more coatings of non-porouspolymers; 2) one or more coatings of a combination of one or more porouspolymers and one or more non-porous polymers; 3) one or more coating ofporous polymer, or 4) one or more combinations of options 1, 2, and 3.As can be appreciated different biological agents can be located inand/or between different polymer coating layers and/or on and/or thestructure of the medical device. As can also be appreciated, many otherand/or additional coating combinations and/or configurations can beused. The concentration of one or more biological agents, the type ofpolymer, the type and/or shape of internal structures in the medicaldevice and/or the coating thickness of one or more biological agents canbe used to control the release time, the release rate and/or the dosageamount of one or more biological agents; however, other or additionalcombinations can be used. As such, the biological agent and polymersystem combination and location on the medical device can be numerous.As can also be appreciated, one or more biological agents can bedeposited on the top surface of the medical device to provide an initialburst effect of the one or more biological agents prior to 1) thecontrol release of the one or more biological agents through one or morelayers of polymer system that include one or more non-porous polymersand/or 2) the uncontrolled release of the one or more biological agentsthrough one or more layers of polymer system. The one or more biologicalagents and/or polymers can be coated on the medical device by a varietyof mechanisms such as, but not limited to, spraying (e.g., atomizingspray techniques, etc.), dip coating, roll coating, sonication,brushing, plasma deposition, and/or depositing by vapor deposition. Thethickness of each polymer layer and/or layer of biological agent isgenerally at least about 0.01 μm and is generally less than about 150μm. In one non-limiting embodiment, the thickness of a polymer layerand/or layer of biological agent is about 0.02-75 μm, more particularlyabout 0.05-50 μm, and even more particularly about 1-30 μm. When themedical device includes and/or is coated with one or more biologicalagents such that at least one of the biological agents is at leastpartially controllably released from the medical device, the need or useof body-wide therapy for extended periods of time can be reduced oreliminated. In the past, the use of body-wide therapy was used by thepatient long after the patient left the hospital or other type ofmedical facility. This body-wide therapy could last days, weeks, monthsor sometimes over a year after surgery. The medical device of thepresent invention can be applied or inserted into a treatment areaand 1) merely requires reduced use and/or extended use of body widetherapy after application or insertion of the medical device or 2) doesnot require use and/or extended use of body wide therapy afterapplication or insertion of the medical device. As can be appreciated,use and/or extended use of body wide therapy can be used afterapplication or insertion of the medical device at the treatment area. Inone non-limiting example, no body-wide therapy is needed after theinsertion of the medical device into a patient. In another and/oralternative non-limiting example, short term use of body-wide therapy isneeded or used after the insertion of the medical device into a patient.Such short term use can be terminated after the release of the patientfrom the hospital or other type of medical facility, or one to two daysor weeks after the release of the patient from the hospital or othertype of medical facility; however, it will be appreciated that othertime periods of body-wide therapy can be used. As a result of the use ofthe medical device of the present invention, the use of body-widetherapy after a medical procedure involving the insertion of a medicaldevice into a treatment area can be significantly reduced or eliminated.

In another and/or alternative non-limiting aspect of the presentinvention, controlled release of one or more biological agents from themedical device, when controlled release is desired, can be accomplishedby using one or more non-porous polymer layers; however, other and/oradditional mechanisms can be used to controllably release the one ormore biological agents. The one or more biological agents are at leastpartially controllably released by molecular diffusion through the oneor more non-porous polymer layers. When one or more non-porous polymerlayers are used, the one or more polymer layers are typicallybiocompatible polymers; however, this is not required. The one or morenon-porous polymers can be applied to the medical device without the useof chemical, solvents, and/or catalysts; however, this is not required.In one non-limiting example, the non-porous polymer can be at leastpartially applied by, but not limited to, vapor deposition and/or plasmadeposition. The non-porous polymer can be selected so as to polymerizeand cure merely upon condensation from the vapor phase; however, this isnot required. The application of the one or more non-porous polymerlayers can be accomplished without increasing the temperature aboveambient temperature (e.g., 65-90° F.); however, this is not required.The non-porous polymer system can be mixed with one or more biologicalagents prior to being coated on the medical device and/or be coated on amedical device that previously included one or more biological agents;however, this is not required. The use of one or more non-porous polymerlayers allow for accurate controlled release of the biological agentfrom the medical device. The controlled release of one or morebiological agents through the non-porous polymer is at least partiallycontrolled on a molecular level utilizing the motility of diffusion ofthe biological agent through the non-porous polymer. In one non-limitingexample, the one or more non-porous polymer layers can include, but arenot limited to, polyamide, parylene (e.g., parylene C, parylene N)and/or a parylene derivative.

In still another and/or alternative non-limiting aspect of the presentinvention, controlled release of one or more biological agents from themedical device, when controlled release is desired, can be accomplishedby using one or more polymers that form a chemical bond with one or morebiological agents. In one non-limiting example, at least one biologicalagent includes trapidil, trapidil derivative or a salt thereof that iscovalently bonded to at least one polymer such as, but not limited to,an ethylene-acrylic acid copolymer. The ethylene is the hydrophobicgroup and acrylic acid is the hydrophilic group. The mole ratio of theethylene to the acrylic acid in the copolymer can be used to control thehydrophobicity of the copolymer. The degree of hydrophobicity of one ormore polymers can be also be used to control the release rate of one ormore biological agents from the one or more polymers. The amount ofbiological agent that can be loaded with one or more polymers may be afunction of the concentration of anionic groups and/or cationic groupsin the one or more polymer. For biological agents that are anionic, theconcentration of biological agent that can be loaded on the one or morepolymers is generally a function of the concentration of cationic groups(e.g. amine groups and the like) in the one or more polymer and thefraction of these cationic groups that can ionically bind to the anionicform of the one or more biological agents. For biological agents thatare cationic (e.g., trapidil, etc.), the concentration of biologicalagent that can be loaded on the one or more polymers is generally afunction of the concentration of anionic groups (i.e., carboxylategroups, phosphate groups, sulfate groups, and/or other organic anionicgroups) in the one or more polymers, and the fraction of these anionicgroups that can ionically bind to the cationic form of the one or morebiological agents. As such, the concentration of one or more biologicalagent that can be bound to the one or more polymers can be varied bycontrolling the amount of hydrophobic and hydrophilic monomer in the oneor more polymers, by controlling the efficiency of salt formationbetween the biological agent, and/or the anionic/cationic groups in theone or more polymers.

In still another and/or alternative non-limiting aspect of the presentinvention, controlled release of one or more biological agents from themedical device, when controlled release is desired, can be accomplishedby using one or more polymers that include one or more inducedcross-links. These one or more cross-links can be used to at leastpartially control the rate of release of the one or more biologicalagents from the one or more polymers. The cross-linking in the one ormore polymers can be instituted by a number to techniques such as, butnot limited to, using catalysts, using radiation, using heat, and/or thelike. The one or more cross-links formed in the one or more polymers canresult in the one or more biological agents to become partially or fullyentrapped within the cross-linking, and/or form a bond with thecross-linking. As such, the partially or fully biological agent takeslonger to release itself from the cross-linking, thereby delaying therelease rate of the one or more biological agents from the one or morepolymers. Consequently, the amount of biological agent, and/or the rateat which the biological agent is released from the medical device overtime can be at least partially controlled by the amount or degree ofcross-linking in the one or more polymers.

In still a further and/or alternative aspect of the present invention, avariety of polymers can be coated on the medical device and/or be usedto form at least a portion of the medical device. The one or morepolymers can be used on the medical for a variety of reasons such as,but not limited to, 1) forming a portion of the medical device, 2)improving a physical property of the medical device (e.g., improvestrength, improve durability, improve bio-compatibility, reducefriction, etc.), 3) forming a protective coating on one or more surfacestructures on the medical device, 4) at least partially forming one ormore surface structures on the medical device, and/or 5) at leastpartially controlling a release rate of one or more biological agentsfrom the medical device. As can be appreciated, the one or more polymerscan have other or additional uses on the medical device. The one or morepolymers can be porous, non-porous, biostable, biodegradable (i.e.,dissolves, degrades, is absorbed, or any combination thereof in thebody), and/or biocompatible. When the medical device is coated with oneor more polymers, the polymer can include 1) one or more coatings ofnon-porous polymers; 2) one or more coatings of a combination of one ormore porous polymers and one or more non-porous polymers; 3) one or morecoatings of one or more porous polymers and one or more coatings of oneor more non-porous polymers; 4) one or more coating of porous polymer,or 5) one or more combinations of options 1, 2, 3 and 4. The thicknessof one or more of the polymer layers can be the same or different. Whenone or more layers of polymer are coated onto at least a portion of themedical device, the one or more coatings can be applied by a variety oftechniques such as, but not limited to, vapor deposition and/or plasmadeposition, spraying, dip-coating, roll coating, sonication,atomization, brushing and/or the like; however, other or additionalcoating techniques can be used. The one or more polymers that can becoated on the medical device and/or used to at least partially form themedical device can be polymers that considered to be biodegradable,bioresorbable, or bioerodable; polymers that are considered to bebiostable; and/or polymers that can be made to be biodegradable and/orbioresorbable with modification. Non-limiting examples of polymers thatare considered to be biodegradable, bioresorbable, or bioerodableinclude, but are not limited to, aliphatic polyesters; poly(glycolicacid) and/or copolymers thereof (e.g., poly(glycolide trimethylenecarbonate); poly(caprolactone glycolide)); poly(lactic acid) and/orisomers thereof (e.g., poly-L(lactic acid) and/or poly-D Lactic acid)and/or copolymers thereof (e.g. DL-PLA), with and without additives(e.g. calcium phosphate glass), and/or other copolymers (e.g.poly(caprolactone lactide), poly(lactide glycolide), poly(lactic acidethylene glycol)); poly(ethylene glycol); poly(ethylene glycol)diacrylate; poly(lactide); polyalkylene succinate; polybutylenediglycolate; polyhydroxybutyrate (PHB); polyhydroxyvalerate (PHV);polyhydroxybutyrate/polyhydroxyvalerate copolymer (PHB/PHV);poly(hydroxybutyrate-co-valerate); polyhydroxyalkaoates (PHA);polycaprolactone; poly(caprolactone-polyethylene glycol) copolymer;poly(valerolactone); polyanhydrides; poly(orthoesters) and/or blendswith polyanhydrides; poly(anhydride-co-imide); polycarbonates(aliphatic); poly(hydroxyl-esters); polydioxanone; polyanhydrides;polyanhydride esters; polycyanoacrylates; poly(alkyl 2-cyanoacrylates);poly(amino acids); poly(phosphazenes); poly(propylene fumarate);poly(propylene fumarate-co-ethylene glycol); poly(fumarate anhydrides);fibrinogen; fibrin; gelatin; cellulose and/or cellulose derivativesand/or cellulosic polymers (e.g., cellulose acetate, cellulose acetatebutyrate, cellulose butyrate, cellulose ethers, cellulose nitrate,cellulose propionate, cellophane); chitosan and/or chitosan derivatives(e.g., chitosan NOCC, chitosan NOOC-G); alginate; polysaccharides;starch; amylase; collagen; polycarboxylic acids; poly(ethylester-co-carboxylate carbonate) (and/or other tyrosine derivedpolycarbonates); poly(iminocarbonate); poly(BPA-iminocarbonate);poly(trimethylene carbonate); poly(iminocarbonate-amide) copolymersand/or other pseudo-poly(amino acids); poly(ethylene glycol);poly(ethylene oxide); poly(ethylene oxide)/poly(butylene terephthalate)copolymer; poly(epsilon-caprolactone-dimethyltrimethylene carbonate);poly(ester amide); poly(amino acids) and conventional synthetic polymersthereof; poly(alkylene oxalates); poly(alkylcarbonate); poly(adipicanhydride); nylon copolyamides; NO-carboxymethyl chitosan NOCC);carboxymethyl cellulose; copoly(ether-esters) (e.g., PEO/PLA dextrans);polyketals; biodegradable polyethers; biodegradable polyesters;polydihydropyrans; polydepsipeptides; polyarylates (L-tyrosine-derived)and/or free acid polyarylates; polyamides (e.g., Nylon 66,polycaprolactam); poly(propylene fumarate-co-ethylene glycol) (e.g.,fumarate anhydrides); hyaluronates; poly-p-dioxanone; polypeptides andproteins; polyphosphoester; polyphosphoester urethane; polysaccharides;pseudo-poly(amino acids); starch; terpolymer; (copolymers of glycolide,lactide, or dimethyltrimethylene carbonate); rayon; rayon triacetate;latex; and/pr copolymers, blends, and/or composites of above.Non-limiting examples of polymers that considered to be biostableinclude, but are not limited to, parylene; parylene c; parylene f;parylene n; parylene derivatives; maleic anyhydride polymers;phosphorylcholine; poly n-butyl methacrylate (PBMA);polyethylene-co-vinyl acetate (PEVA); PBMA/PEVA blend or copolymer;polytetrafluoroethene (Teflon®) and derivatives; poly-paraphenyleneterephthalamide (Kevlar®); poly(ether ether ketone) (PEEK);poly(styrene-b-isobutylene-b-styrene) (Translute™);tetramethyldisiloxane (side chain or copolymer); polyimidespolysulfides; poly(ethylene terephthalate); poly(methyl methacrylate);poly(ethylene-co-methyl methacrylate); styrene-ethylene/butylene-styreneblock copolymers; ABS; SAN; acrylic polymers and/or copolymers (e.g.,n-butyl-acrylate, n-butyl methacrylate, 2-ethylhexyl acrylate,lauryl-acrylate, 2-hydroxy-propyl acrylate, polyhydroxyethyl,methacrylate/methylmethacrylate copolymers); glycosaminoglycans; alkydresins; elastin; polyether sulfones; epoxy resin; poly(oxymethylene);polyolefins; polymers of silicone; polymers of methane; polyisobutylene;ethylene-alphaolefin copolymers; polyethylene; polyacrylonitrile;fluorosilicones; poly(propylene oxide); polyvinyl aromatics (e.g.polystyrene); poly(vinyl ethers) (e.g. polyvinyl methyl ether);poly(vinyl ketones); poly(vinylidene halides) (e.g. polyvinylidenefluoride, polyvinylidene chloride); poly(vinylpyrolidone);poly(vinylpyrolidone)/vinyl acetate copolymer; polyvinylpridineprolastin or silk-elastin polymers (SELP); silicone; silicone rubber;polyurethanes (polycarbonate polyurethanes, silicone urethane polymer)(e.g., chronoflex varieties, bionate varieties); vinyl halide polymersand/or copolymers (e.g. polyvinyl chloride); polyacrylic acid; ethyleneacrylic acid copolymer; ethylene vinyl acetate copolymer; polyvinylalcohol; poly(hydroxyl alkylmethacrylate); Polyvinyl esters (e.g.polyvinyl acetate); and/or copolymers, blends, and/or composites ofabove. Non-limiting examples of polymers that can be made to bebiodegradable and/or bioresorbable with modification include, but arenot limited to, hyaluronic acid (hyanluron); polycarbonates;polyorthocarbonates; copolymers of vinyl monomers; polyacetals;biodegradable polyurethanes; polyacrylamide; polyisocyanates; polyamide;and/or copolymers, blends, and/or composites of above. As can beappreciated, other and/or additional polymers and/or derivatives of oneor more of the above listed polymers can be used. The one or morepolymers can be coated on the medical device by a variety of mechanismssuch as, but not limited to, spraying (e.g., atomizing spray techniques,etc.), dip coating, roll coating, sonication, brushing, plasmadeposition, and/or depositing by vapor deposition. The thickness of eachpolymer layer is generally at least about 0.01 μm and is generally lessthan about 150 μm; however, other thicknesses can be used. In onenon-limiting embodiment, the thickness of a polymer layer and/or layerof biological agent is about 0.02-75 μm, more particularly about 0.05-50μm, and even more particularly about 1-30 μm. As can be appreciated,other thicknesses can be used. In one non-limiting embodiment, themedical device includes and/or is coated with parylene, PLGA, POE, PGA,PLLA, PAA, PEG, chitosan and/or derivatives of one or more of thesepolymers. In another and/or alternative non-limiting embodiment, themedical device includes and/or is coated with a non-porous polymer thatincludes, but is not limited to, polyamide, parylene c, parylene nand/or a parylene derivative. In still another and/or alternativenon-limiting embodiment, the medical device includes and/or is coatedwith poly(ethylene oxide), poly(ethylene glycol), and poly(propyleneoxide), polymers of silicone, methane, tetrafluoroethylene (includingTEFLON brand polymers), tetramethyldisiloxane, and the like.

In another and/or alternative non-limiting aspect of the presentinvention, the medical device, when including and/or is coated with oneor more biological agents, can include and/or can be coated with one ormore biological agents that are the same or different in differentregions of the medical device and/or have differing amounts and/orconcentrations in differing regions of the medical device. For instance,the medical device can a) be coated with and/or include one or morebiologicals on at least one portion of the medical device and at leastanother portion of the medical device is not coated with and/or includesbiological agent; b) be coated with and/or include one or morebiologicals on at least one portion of the medical device that isdifferent from one or more biologicals on at least another portion ofthe medical device; c) be coated with and/or include one or morebiologicals at a concentration on at least one portion of the medicaldevice that is different from the concentration of one or morebiologicals on at least another portion of the medical device; etc.

In still another and/or alternative non-limiting aspect of the presentinvention, one or more surfaces of the medical device can be treated toachieve the desired coating properties of the one or more biologicalagents and one or more polymers coated on the medical device. Suchsurface treatment techniques include, but are not limited to, cleaning,buffing, smoothing, etching (chemical etching, plasma etching, etc.),etc. When an etching process is used, various gasses can be used forsuch a surface treatment process such as, but not limited to, carbondioxide, nitrogen, oxygen, Freon, helium, hydrogen, etc. The plasmaetching process can be used to clean the surface of the medical device,change the surface properties of the medical device so as to affect theadhesion properties, lubricity properties, etc. of the surface of themedical device. As can be appreciated, other or additional surfacetreatment processes can be used prior to the coating of one or morebiological agents and/or polymers on the surface of the medical device.In one non-limiting manufacturing process, one or more portions of themedical device are cleaned and/or plasma etched; however, this is notrequired. Plasma etching can be used to clean the surface of the medicaldevice, and/or to form one or more non-smooth surfaces on the medicaldevice to facilitate in the adhesion of one or more coatings ofbiological agents and/or one or more coatings of polymer on the medicaldevice. The gas for the plasma etching can include carbon dioxide and/orother gasses. Once one or more surface regions of the medical devicehave been treated, one or more coatings of polymer and/or biologicalagent can be applied to one or more regions of the medical device. Forinstance, 1) one or more layers of porous or non-porous polymer can becoated on an outer and/or inner surface of the medical device, 2) one ormore layers of biological agent can be coated on an outer and/or innersurface of the medical device, or 3) one or more layers of porous ornon-porous polymer that includes one or more biological agents can becoated on an outer and/or inner surface of the medical device. The oneor more layers of biological agent can be applied to the medical deviceby a variety of techniques (e.g., dipping, rolling, brushing, spraying,particle atomization, etc.). One non-limiting coating technique is by anultrasonic mist coating process wherein ultrasonic waves are used tobreak up the droplet of biological agent and form a mist of very finedroplets. These fine droplets have an average droplet diameter of about0.1-3 microns. The fine droplet mist facilitates in the formation of auniform coating thickness and can increase the coverage area on themedical device.

In still yet another and/or alternative non-limiting aspect of thepresent invention, one or more portions of the medical device can 1)include the same or different biological agents, 2) include the same ordifferent amount of one or more biological agents, 3) include the sameor different polymer coatings, 4) include the same or different coatingthicknesses of one or more polymer coatings, 5) have one or moreportions of the medical device controllably release and/oruncontrollably release one or more biological agents, and/or 6) have oneor more portions of the medical device controllably release one or morebiological agents and one or more portions of the medical deviceuncontrollably release one or more biological agents.

In yet another and/or alternative non-limiting aspect of the invention,the medical device can include a marker material that facilitatesenabling the medical device to be properly positioned in a bodypassageway. The marker material is typically designed to be visible toelectromagnetic waves (e.g., x-rays, microwaves, visible light, inferredwaves, ultraviolet waves, etc.); sound waves (e.g., ultrasound waves,etc.); magnetic waves (e.g., MRI, etc.); and/or other types ofelectromagnetic waves (e.g., microwaves, visible light, inferred waves,ultraviolet waves, etc.). In one non-limiting embodiment, the markermaterial is visible to x-rays (i.e., radiopaque). The marker materialcan form all or a portion of the medical device and/or be coated on oneor more portions (flaring portion and/or body portion; at ends ofmedical device; at or near transition of body portion and flaringsection; etc.) of the medical device. The location of the markermaterial can be on one or multiple locations on the medical device. Thesize of the one or more regions that include the marker material can bethe same or different. The marker material can be spaced at defineddistances from one another so as to form ruler like markings on themedical device to facilitate in the positioning of the medical device ina body passageway. The marker material can be a rigid or flexiblematerial. The marker material can be a biostable or biodegradablematerial. When the marker material is a rigid material, the markermaterial is typically formed of a metal material (e.g., metal band,metal plating, etc.); however, other or additional materials can beused. The metal which at least partially forms the medical device canfunction as a marker material; however, this is not required. When themarker material is a flexible material, the marker material typically isformed of one or more polymers that are marker materialsin-of-themselves and/or include one or more metal powders and/or metalcompounds. In one non-limiting embodiment, the flexible marker materialincludes one or more metal powders in combinations with parylene, PLGA,POE, PGA, PLLA, PAA, PEG, chitosan and/or derivatives of one or more ofthese polymers. In another and/or alternative non-limiting embodiment,the flexible marker material includes one or more metals and/or metalpowders of aluminum, barium, bismuth, cobalt, copper, chromium, gold,iron, stainless steel, titanium, vanadium, nickel, zirconium, niobium,lead, molybdenum, platinum, yttrium, calcium, rare earth metals,rhenium, zinc, silver, depleted radioactive elements, tantalum and/ortungsten; and/or compounds thereof. The marker material can be coatedwith a polymer protective material; however, this is not required. Whenthe marker material is coated with a polymer protective material, thepolymer coating can be used to 1) at least partially insulate the markermaterial from body fluids, 2) facilitate in retaining the markermaterial on the medical device, 3) at least partially shielding themarker material from damage during a medical procedure and/or 4) providea desired surface profile on the medical device. As can be appreciated,the polymer coating can have other or additional uses. The polymerprotective coating can be a biostable polymer or a biodegradable polymer(e.g., degrades and/or is absorbed). The coating thickness of theprotective coating polymer material, when used, is typically less thanabout 300 microns; however, other thickness can be used. In onenon-limiting embodiment, the protective coating materials includeparylene, PLGA, POE, PGA, PLLA, PAA, PEG, chitosan and/or derivatives ofone or more of these polymers.

In still another and/or alternative aspect of the invention, the medicaldevice can be an expandable device that can be expanded by use ofanother device (e.g., balloon, etc.) and/or is self expanding. Theexpandable medical device can be fabricated from a material that has noor substantially no shape memory characteristics or can be fabricatedfrom a material having shape-memory characteristics.

In a further and/or alternative non-limiting aspect of the presentinvention, the medical device or one or more regions of the medicaldevice can be constructed by use of one or more microelectromechanicalmanufacturing techniques (MEMS (e.g., micro-machining, lasermicro-machining, laser micro-machining, micro-molding, etc.); however,other or additional manufacturing techniques can be used. The medicaldevice can include one or more surface structures (e.g., pore, channel,pit, rib, slot, notch, bump, teeth, well, hole, groove, etc.). Thesestructures can be at least partially formed by MEMS (e.g.,micro-machining, etc.) technology and/or other types of technology. Themedical device can include one or more micro-structures (e.g.,micro-needle, micro-pore, micro-cylinder, micro-cone, micro-pyramid,micro-tube, micro-parallelopiped, micro-prism, micro-hemisphere, teeth,rib, ridge, ratchet, hinge, zipper, zip-tie like structure, etc.) on thesurface of the medical device. Non-limiting examples of structures thatcan be formed on the medical devices such as stents are illustrated inUnited States Patent Publication Nos. 2004/0093076 and 2004/0093077,which are incorporated herein by reference. Typically, themicro-structures, when formed, extend from or into the outer surface nomore than about 400 microns, and more typically less than about 300microns, and more typically about 15-250 microns; however, other sizescan be used. The micro-structures can be clustered together or disbursedthroughout the surface of the medical device. Similar shaped and/orsized micro-structures and/or surface structures can be used, ordifferent shaped and/or sized micro-structures can be used. When one ormore surface structures and/or micro-structures are designed to extendfrom the surface of the medical device, the one or more surfacestructures and/or micro-structures can be formed in the extendedposition and/or be designed so as to extend from the medical deviceduring and/or after deployment of the medical device in a treatmentarea. The micro-structures and/or surface structures can be designed tocontain and/or be fluidly connected to a passageway, cavity, etc.;however, this is not required. The one or more surface structures and/ormicro-structures can be used to engage and/or penetrate surroundingtissue or organs once the medical device has be position on and/or in apatient; however, this is not required. The one or more surfacestructures and/or micro-structures can be used to facilitate in formingmaintaining a shape of a medical device (i.e., see devices in UnitedStates Patent Publication Nos. 2004/0093076 and 2004/0093077). The oneor more surface structures and/or micro-structures can be at leastpartially formed by MEMS (e.g., micro-machining, laser micro-machining,micro-molding, etc.) technology; however, this is not required. In onenon-limiting embodiment, the one or more surface structures and/ormicro-structures can be at least partially formed of a biological agentand/or be formed of a polymer. One or more of the surface structuresand/or micro-structures can include one or more internal passagewaysthat can include one or more materials (e.g., biological agent, polymer,etc.); however, this is not required. The one or more surface structuresand/or micro-structures can be formed by a variety of processes (e.g.,machining, chemical modifications, chemical reactions, MEMS (e.g.,micro-machining, etc.), etching, laser cutting, etc.). The one or morecoatings and/or one or more surface structures and/or micro-structuresof the medical device can be used for a variety of purposes such as, butnot limited to, 1) increasing the bonding and/or adhesion of one or morebiological agents, adhesives, marker materials and/or polymers to themedical device, 2) changing the appearance or surface characteristics ofthe medical device, and/or 3) controlling the release rate of one ormore biological agents. The one or more micro-structures and/or surfacestructures can be biostable, biodegradable, bioabsorbable, etc. One ormore regions of the medical device that are at least partially formed bymicroelectromechanical manufacturing techniques can be biostable,biodegradable, bioabsorbable, etc. The medical device or one or moreregions of the medical device can be at least partially covered and/orfilled with a protective material so to at least partially protect oneor more regions of the medical device, and/or one or moremicro-structures and/or surface structures on the medical device fromdamage. One or more regions of the medical device, and/or one or moremicro-structures and/or surface structures on the medical device can bedamaged when the medical device is 1) packaged and/or stored, 2)unpackaged, 3) connected to and/or other secured and/or placed onanother medical device, 4) inserted into a treatment area, 5) handled bya user, and/or 6) form a barrier between one or more micro-structuresand/or surface structures and fluids in the body passageway. As can beappreciated, the medical device can be damaged in other or additionalways. The protective material can be used to protect the medical deviceand one or more micro-structures and/or surface structures from suchdamage. The protective material can include one or more polymerspreviously identified above. The protective material can be 1) biostableand/or biodegradable and/or 2) porous and/or non-porous. In onenon-limiting design, the polymer is at least partially biodegradable soas to at least partially exposed one or more micro-structure and/orsurface structure to the environment after the medical device has beenat least partially inserted into a treatment area. In another and/oradditional non-limiting design, the protective material includes, but isnot limited to, sugar (e.g., glucose, fructose, sucrose, etc.),carbohydrate compound, salt (e.g., NaCl, etc.), parylene, PLGA, POE,PGA, PLLA, PAA, PEG, chitosan and/or derivatives of one or more of thesematerials; however, other and/or additional materials can be used. Instill another and/or additional non-limiting design, the thickness ofthe protective material is generally less than about 300 microns, andtypically less than about 150 microns; however, other thicknesses can beused. The protective material can be coated by one or more mechanismspreviously described herein.

In still yet another and/or alternative non-limiting aspect of thepresent invention, the medical device can include and/or be used with aphysical hindrance. The physical hindrance can include, but is notlimited to, an adhesive, a sheath, a magnet, tape, wire, string, etc.The physical hindrance can be used to 1) physically retain one or moreregions of the medical device in a particular form or profile, 2)physically retain the medical device on a particular deployment device,3) protect one or more surface structures and/or micro-structures on themedical device, and/or 4) form a barrier between one or more surfaceregions, surface structures and/or micro-structures on the medicaldevice and the fluids in a body passageway. As can be appreciated, thephysical hindrance can have other and/or additional functions. Thephysical hindrance is typically a biodegradable material; however, abiostable material can be used. The physical hindrance can be designedto withstand sterilization of the medical device; however, this is notrequired. The physical hindrance can be applied to, included in and/orbe used in conjunction with one or more medical devices. Additionally oralternatively, the physical hindrance can be designed to be used withand/or conjunction with a medical device for a limited period of timeand then 1) disengage from the medical device after the medical devicehas been partially or fully deployed and/or 2) dissolve and/or degradeduring and/or after the medical device has been partially or fullydeployed; however, this is not required. Additionally or alternatively,the physical hindrance can be designed and be formulated to betemporarily used with a medical device to facilitate in the deploymentof the medical device; however, this is not required. In onenon-limiting use of the physical hindrance, the physical hindrance isdesigned or formulated to at least partially secure a medical device toanother device that is used to at least partially transport the medicaldevice to a location for treatment. In another and/or alternativenon-limiting use of the physical hindrance, the physical hindrance isdesigned or formulated to at least partially maintain the medical devicein a particular shape or form until the medical device is at leastpartially positioned in a treatment location. In still another and/oralternative non-limiting use of the physical hindrance, the physicalhindrance is designed or formulated to at least partially maintainand/or secure one type of medical device to another type of medicalinstrument or device until the medical device is at least partiallypositioned in a treatment location. The physical hindrance can also oralternatively be designed and formulated to be used with a medicaldevice to facilitate in the use of the medical device. In onenon-limiting use of the physical hindrance, when in the form of anadhesive, can be formulated to at least partially secure a medicaldevice to a treatment area so as to facilitate in maintaining themedical device at the treatment area. For instance, the physicalhindrance can be used in such use to facilitate in maintaining a medicaldevice on or at a treatment area until the medical device is properlysecured to the treatment area by sutures, stitches, screws, nails, rod,etc; however, this is not required. Additionally or alternatively, thephysical hindrance can be used to facilitate in maintaining a medicaldevice on or at a treatment area until the medical device has partiallyor fully accomplished its objective. The physical hindrance is typicallya biocompatible material so as to not cause unanticipated adverseeffects when properly used. The physical hindrance can be biostable orbiodegradable (e.g., degrades and/or is absorbed, etc.). When thephysical hindrance includes or is one or more adhesives, the one or moreadhesives can be applied to the medical device by, but is not limitedto, spraying (e.g., atomizing spray techniques, etc.), dip coating, rollcoating, sonication, brushing, plasma deposition, and/or depositing byvapor deposition, brushing, painting, etc.) on the medical device. Thephysical hindrance can also or alternatively form at least a part of themedical device. One or more regions and/or surfaces of a medical devicecan also or alternatively include the physical hindrance. The physicalhindrance can include one or more biological agents and/or othermaterials (e.g., marker material, polymer, etc.); however, this is notrequired. When the physical hindrance is or includes an adhesive, theadhesive can be formulated to controllably release one or morebiological agents in the adhesive and/or coated on and/or containedwithin the medical device; however, this is not required. The adhesivecan also or alternatively control the release of one or more biologicalagents located on and/or contained in the medical device by forming apenetrable or non-penetrable barrier to such biological agents; however,this is not required. The adhesive can include and/or be mixed with oneor more polymers; however, this is not required. The one or morepolymers can be used to 1) control the time of adhesion provided by saidadhesive, 2) control the rate of degradation of the adhesive, and/or 3)control the rate of release of one or more biological agents from theadhesive and/or diffusing or penetrating through the adhesive layer;however, this is not required. When the physical hindrance includes asheath, the sheath can be designed to partially or fully encircle themedical device. The sheath can be designed to be physically removed fromthe medical device after the medical device is deployed to a treatmentarea; however, this is not required. The sheath can be formed of abiodegradable material that at least partially degrades overtime to atleast partially expose one or more surface regions, micro-structuresand/or surface structures of the medical device; however, this is notrequired. The sheath can include and/or be at least partially coatedwith one or more biological agents. The sheath include one or morepolymers; however, this is not required. The one or more polymers can beused for a variety of reasons such as, but not limited to, 1) forming aportion of the sheath, 2) improving a physical property of the sheath(e.g., improve strength, improve durability, improve biocompatability,reduce friction, etc.), and/or 3 at least partially controlling arelease rate of one or more biological agents from the sheath. As can beappreciated, the one or more polymers can have other or additional useson the sheath.

In still a further and/or alternative non-limiting aspect of the presentinvention, the medical device can be fully or partially formed of a basematerial that has biostable or bioabsorbable properties. The medicaldevice can be at least partially formed of one or more polymers,biological agents, metals (e.g., aluminum, barium, bismuth, calcium,carbon, cobalt, copper, chromium, depleted radioactive elements, gold,iron, lead, molybdenum, magnesium, nickel, niobium, platinum, rare earthmetals, rhenium, silver, tantalum, titanium, tungsten, vanadium,yttrium, zinc, zirconium, and/or alloys thereof (e.g., stainless steel,nitinol, Cr—Co, Mo—Re, Ta—W, Mg—Zr, Mg—Zn, brass, etc.)), ceramics,and/or fiber reinforced materials (e.g., carbon fiber material,fiberglass, etc.). The medical device generally includes one or morematerials that impart the desired properties to the medical device so asto withstand the manufacturing process that is needed to produce themedical device. These manufacturing processes can include, but are notlimited to, laser cutting, etching, grinding, water cutting, sparkerosion, crimping, annealing, drawing, pilgering, electroplating,electro-polishing, chemical polishing, ion beam deposition orimplantation, sputter coating, vacuum deposition, etc.

In still a further and/or alternative non-limiting aspect of the presentinvention, the medical device can be fully or partially formed of a basematerial that is at least partially made of a novel metal alloy havingimproved properties as compared to past medical devices that were formof stainless steel, or cobalt-chromium alloys. The novel metal alloyused to at least partially form the medical device can improve one ormore properties (e.g., strength, durability, hardness, biostability,bendability, coefficient of friction, radial strength, flexibility,tensile strength, longitudinal lengthening, stress-strain properties,improved recoil properties, radiopacity, heat sensitivity,biocompatibility, etc.) of such medical device. These one or morephysical properties of the novel metal alloy can be achieved in themedical device without increasing the bulk, volume or weight of themedical device, and in some instances can be obtained even when thevolume, bulk and/or weight of the medical device is reduced as comparedto medical devices that are at least partially formed from traditionalstainless steel or cobalt and chromium alloy materials. The novel metalalloy that is used to at least partially form the medical device canthus 1) increase the radiopacity of the medical device, 2) increase theradial strength of the medical device, 3) increase the tensile strengthof the medical device, 4) improve the stress-strain properties of themedical device, 5) improve the crimping and/or expansion properties ofthe medical device, 6) improve the bendability and/or flexibility of themedical device, 7) improve the strength and/or durability of the medicaldevice, 8) increase the hardness of the medical device, 9) improve thelongitudinal lengthening properties of the medical device, 10) improvedrecoil properties of the medical device, 11) improve the frictioncoefficient of the medical device, 12) improve the heat sensitivityproperties of the medical device, 13) improve the biostability and/orbiocompatibility properties of the medical device, and/or 14) enablesmaller, thinner and/or lighter weight medical devices to be made. It isbelieved that a smaller, thinner and/or lighter weight medical devicesuch as, but not limited to a stent, can be inserted in a bodypassageway and result in a decreased incidence of thrombosis. It isbelieved that such a medical device will result in a less adverseresponse by the body when the medical device is inserted in the bodypassageway. As such, the medical device can be used without anybiological agent included in, contained in, and/or coated on the medicaldevice and still result in a reduction in the incidence of thrombosis.As such, the need for extended use of body wide aggressive anti-plateletand/or anti-coagulation therapy after the medical device has beeninserted in the treatment area can be reduced or eliminated by use ofthe novel alloy.

In a further and/or alternative one non-limiting aspect of theinvention, the novel metal alloy that is used to form all or a portionof the medical device includes rhenium and molybdenum. The novel alloycan include one or more other metals such as, but not limited to,calcium, chromium, cobalt, copper, gold, iron, lead, magnesium, nickel,niobium, platinum, rare earth metals, silver, tantalum, titanium,tungsten, yttrium, zinc, zirconium, and/or alloys thereof. In onenon-limiting embodiment of the invention, the novel metal alloy that isused to form all or a portion of the medical device is a novel metalalloy that includes at least about 90 weight percent molybdenum andrhenium. In one non-limiting composition, the content of molybdenum andrhenium in the novel metal alloy is at least about 95 weight percent. Inanother and/or alternative non-limiting composition, the content ofmolybdenum and rhenium in the novel metal alloy is at least about 97weight percent. In still another and/or alternative non-limitingcomposition, the content of molybdenum and rhenium in the novel metalalloy is at least about 98 weight percent. In yet another and/oralternative non-limiting composition, the content of molybdenum andrhenium in the novel metal alloy is at least about 99 weight percent. Instill yet another and/or alternative non-limiting composition, thecontent of molybdenum and rhenium in the novel metal alloy is at leastabout 99.5 weight percent. In a further one non-limiting composition,the content of molybdenum and rhenium in the novel metal alloy is atleast about 99.9 weight percent. In still a further and/or alternativenon-limiting composition, the content of molybdenum and rhenium in thenovel metal alloy is at least about 99.95 weight percent. In yet afurther and/or alternative non-limiting composition, the content ofmolybdenum and rhenium in the novel metal alloy is at least about 99.99weight percent. As can be appreciated, other weight percentages of therhenium and molybdenum content of the novel metal alloy can be used. Inone non-limiting composition, the purity level of the novel metal alloyis such so as to produce a solid solution of the novel metal alloy. Asolid solution or homogeneous solution is defined as a metal alloy thatincludes two or more primary metals and the combined weight percent ofthe primary metals is at least about 95 weight percent, typically atleast about 99 weight percent, more typically at least about 99.5 weightpercent, even more typically at least about 99.8 weight percent, andstill even more typically at least about 99.9 weight percent. A primarymetal is a metal component of the metal alloy that is not a metalimpurity. A solid solution of a novel metal alloy that includes rheniumand molybdenum as the primary metals is an alloy that includes at leastabout 95-99 weight percent rhenium and molybdenum. It is believed that apurity level of less than 95 weight percent molybdenum and rheniumadversely affects one or more physical properties of the metal alloythat are useful or desired in forming and/or using a medical device. Inone embodiment of the invention, the rhenium content of the novel metalalloy in accordance with the present invention is at least about 40weight percent. In one non-limiting composition, the rhenium content ofthe novel metal alloy is at least about 45 weight percent. In stillanother and/or alternative non-limiting composition, the rhenium contentof the novel metal alloy is about 45-50 weight percent. In yet anotherand/or alternative non-limiting composition, the rhenium content of thenovel metal alloy is about 47-48 weight percent. As can be appreciated,other weight percentages of the rhenium content of the novel metal alloycan be used. In another and/or alternative embodiment of the invention,the molybdenum content of the novel metal alloy in accordance with thepresent invention is at least about 40 weight percent. In onenon-limiting composition, the molybdenum content of the novel metalalloy is at least about 45 weight percent. In another and/or alternativenon-limiting composition, the molybdenum content of the novel metalalloy is at least about 50 weight percent. In still another and/oralternative non-limiting composition, the molybdenum content of thenovel metal alloy is about 50-60 percent. In yet another and/oralternative non-limiting composition, the molybdenum content of thenovel metal alloy is about 50-56 weight percent. As can be appreciated,other weight percentages of the molybdenum content of the novel metalalloy can be used. The novel metal alloy can include controlled amountsof at least one additional metal which includes titanium, yttrium,and/or zirconium; however, this is not required. The addition ofcontrolled amounts of titanium, yttrium, and/or zirconium to themolybdenum and rhenium alloy has been found to form a metal alloy thathas improved physical properties over a metal alloy that principallyincludes molybdenum and rhenium. For instance, the addition ofcontrolled amounts of titanium, yttrium, and/or zirconium to themolybdenum and rhenium alloy can result in 1) an increase in yieldstrength of the alloy as compared to a metal alloy that principallyincludes molybdenum and rhenium, 2) an increase in tensile elongation ofthe alloy as compared to a metal alloy that principally includesmolybdenum and rhenium, 3) an increase in ductility of the alloy ascompared to a metal alloy that principally includes molybdenum andrhenium, 4) a reduction in grain size of the alloy as compared to ametal alloy that principally includes molybdenum and rhenium, 5) areduction in the amount of free carbon, oxygen and/or nitrogen in thealloy as compared to a metal alloy that principally includes molybdenumand rhenium, and/or 6) a reduction in the tendency of the alloy to formmicro-cracks during the forming of the alloy into a medical device ascompared to the forming of a medical device from a metal alloy thatprincipally includes molybdenum and rhenium. The combined content oftitanium, yttrium and zirconium in the novel metal alloy, when used, isless than about 5 weight percent, typically no more than about 1 weightpercent, and more typically no more than about 0.5 weight percent. Ahigher weight percent content of titanium, yttrium and/or zirconium inthe novel metal alloy can begin to adversely affect the brittleness ofthe novel metal alloy. When titanium is included in the novel metalalloy, the titanium content is typically less than about 1 weightpercent, more typically less than about 0.6 weight percent, even moretypically about 0.05-0.5 weight percent, still even more typically about0.1-0.5 weight percent. As can be appreciated, other weight percentagesof the titanium content of the novel metal alloy can be used. Whenzirconium is included in the novel metal alloy, the zirconium content istypically less than about 0.5 weight percent, more typically less thanabout 0.3 weight percent, even more typically about 0.01-0.25 weightpercent, still even more typically about 0.05-0.25 weight percent. Ascan be appreciated, other weight percentages of the zirconium content ofthe novel metal alloy can be used. When titanium and zirconium areincluded in the novel metal alloy, the weight ratio of titanium tozirconium is about 1-10:1, typically about 1.5-5:1, and more typicallyabout 1.75-2.5:1. When yttrium is included in the novel metal alloy, theyttrium content is typically less than about 0.3 weight percent, moretypically less than about 0.2 weight percent, and even more typicallyabout 0.01-0.1 weight percent. As can be appreciated, other weightpercentages of the yttrium content of the novel metal alloy can be used.The inclusion of titanium, yttrium and/or zirconium in the novel metalalloy is believed to result in a reduction of oxygen trapped in thesolid solution of the novel metal alloy. The reduction of trapped oxygenenables the formation of a smaller grain size in the novel metal alloyand/or an increase in the ductility of the novel metal alloy. Thereduction of trapped oxygen in the novel metal alloy can also increasethe yield strength of the novel metal alloy as compared to alloys ofonly molybdenum and rhenium (i.e., 2-10% increase). The inclusion oftitanium, yttrium and/or zirconium in the novel metal alloy is alsobelieved to cause a reduction in the trapped free carbon in the novelmetal alloy. The inclusion of titanium, yttrium and/or zirconium in thenovel metal alloy is believed to form carbides with the free carbon inthe novel metal alloy. This carbide formation is also believed toimprove the ductility of the novel metal alloy and to also reduce theincidence of cracking during the forming of the metal alloy into amedical device (e.g., stent, etc.). As such, the novel metal alloyexhibits increased tensile elongation as compared to alloys of onlymolybdenum and rhenium (i.e., 1-8% increase). The inclusion of titanium,yttrium and/or zirconium in the novel metal alloy is also believed tocause a reduction in the trapped free nitrogen in the novel metal alloy.The inclusion of titanium, yttrium and/or zirconium in the novel metalalloy is believed to form carbo-nitrides with the free carbon and freenitrogen in the novel metal alloy. This carbo-nitride formation is alsobelieved to improve the ductility of the novel metal alloy and to alsoreduce the incidence of cracking during the forming of the metal alloyinto a medical device (e.g., stent, etc.). As such, the novel metalalloy exhibits increased tensile elongation as compared to alloys ofonly molybdenum and rhenium (i.e., 1-8% increase). The reduction in theamount of free carbon, oxygen and/or nitrogen in the novel metal alloyis also believed to increase the density of the novel metal alloy (i.e.,1-5% increase). The formation of carbides, carbo-nitrides, and/or oxidesin the novel metal alloy results in the formation of dispersed secondphase particles in the novel metal alloy, thereby facilitating in theformation of small grain sizes in the metal alloy. The novel metal alloyincludes less than about 5 weight percent other metals and/orimpurities. A high purity level of the novel metal alloy results in theformation of a more homogeneous alloy, which in turn results in a moreuniform density throughout the novel metal alloy, and also results inthe desired yield and ultimate tensile strengths of the novel metalalloy. The density of the novel metal alloy is generally at least about12 gm/cc, and typically at least about 13-13.5 gm/cc. This substantiallyuniform high density of the novel metal alloy significantly improves theradiopacity of the novel metal alloy. In one non-limiting composition,the novel metal alloy includes less than about 1 weight percent othermetals and/or impurities. In another and/or alternative non-limitingcomposition, the novel metal alloy includes less than about 0.5 weightpercent other metals and/or impurities. In still another and/oralternative non-limiting composition, the novel metal alloy includesless than about 0.4 weight percent other metals and/or impurities. Inyet another and/or alternative non-limiting composition, the novel metalalloy includes less than about 0.2 weight percent other metals and/orimpurities. In still yet another and/or alternative non-limitingcomposition, the novel metal alloy includes less than about 0.1 weightpercent other metals and/or impurities. In a further and/or alternativenon-limiting composition, the novel metal alloy includes less than about0.05 weight percent other metals and/or impurities. In still a furtherand/or alternative non-limiting composition, the novel metal alloyincludes less than about 0.02 weight percent other metals and/orimpurities. In yet a further and/or alternative non-limitingcomposition, the novel metal alloy includes less than about 0.01 weightpercent other metals and/or impurities. As can be appreciated, otherweight percentages of the amount of other metals and/or impurities inthe novel metal alloy can exist. The novel metal alloy includes acertain amount of carbon and oxygen. These two elements have been foundto affect the forming properties and brittleness of the novel metalalloy. The controlled atomic ratio of carbon and oxygen in the novelmetal alloy also can be used to minimize the tendency of the novel metalalloy to form micro-cracks during the forming of the novel alloy into amedical device, and/or during the use and/or expansion of the medicaldevice in a body passageway. In one non-limiting embodiment of theinvention, the novel metal alloy includes up to about 200 ppm carbon andup to about 150 ppm oxygen. Higher carbon and oxygen contents in thenovel metal alloy are believed to adversely affect one or more physicalproperties of the metal alloy that are useful or desired in formingand/or using a medical device. In one non-limiting formulation, thenovel metal alloy includes up to about 150 ppm carbon. In still anotherand/or alternative non-limiting formulation, the novel metal alloyincludes up to about 100 ppm carbon. In yet another and/or alternativenon-limiting formulation, the novel metal alloy includes less than about50 ppm carbon. In still yet another and/or alternative non-limitingformulation, the novel metal alloy includes up to about 100 ppm oxygen.In a further and/or alternative non-limiting formulation, the novelmetal alloy includes up to about 75 ppm oxygen. In still a furtherand/or alternative non-limiting formulation, the novel metal alloyincludes up to about 50 ppm oxygen. In yet a further and/or alternativenon-limiting formulation, the novel metal alloy includes up to about 30ppm oxygen. In still yet a further and/or alternative non-limitingformulation, the novel metal alloy includes less than about 20 ppmoxygen. In yet a further and/or alternative non-limiting formulation,the novel metal alloy includes less than about 10 ppm oxygen. As can beappreciated, other amounts of carbon and/or oxygen in the novel metalalloy can exist. In another and/or alternative non-limiting embodimentof the invention, the carbon to oxygen atomic ratio in the novel metalalloy is generally at least about 2:1 (i.e., weight ratio of about1.5:1). The control of the atomic ratio of carbon to oxygen in the novelmetal alloy allows for the redistribution of oxygen in the metal alloyso as to minimize the tendency of micro-cracking in the novel metalalloy during the forming of the novel alloy into a medical device,and/or during the use and/or expansion of the medical device in a bodypassageway. When the carbon to oxygen atomic ratio falls below 2-2.5:1(i.e., weight ratio of about 1.5-1.88:1), the degree of elongation ofthe novel metal alloy decreases and the incidence of micro-crackingincreases, thus adversely affecting one or more physical properties ofthe metal alloy that are useful or desired in forming and/or using themedical device. In one non-limiting formulation, the carbon to oxygenatomic ratio in the novel metal alloy is generally at least about 2.5:1(i.e., weight ratio of about 1.88:1). In another and/or alternativenon-limiting formulation, the carbon to oxygen atomic ratio in the novelmetal alloy is generally at least about 3:1 (i.e., weight ratio of about2.25:1). In still another and/or alternative non-limiting formulation,the carbon to oxygen atomic ratio in the novel metal alloy is generallyat least about 4:1 (i.e., weight ratio of about 3:1). In yet anotherand/or alternative non-limiting formulation, the carbon to oxygen atomicratio in the novel metal alloy is generally at least about 5:1 (i.e.,weight ratio of about 3.75:1). In still yet another and/or alternativenon-limiting formulation, the carbon to oxygen atomic ratio in the novelmetal alloy is generally about 2.5-50:1 (i.e., weight ratio of about1.88-37.54:1). In a further and/or alternative non-limiting formulation,the carbon to oxygen atomic ratio in the novel metal alloy is generallyabout 2.5-20:1 (i.e., weight ratio of about 1.88-15:1). In still afurther and/or alternative non-limiting formulation, the carbon tooxygen atomic ratio in the novel metal alloy is generally about 2.5-10:1(i.e., weight ratio of about 1.88-7.5:1). In yet a further and/oralternative non-limiting formulation, the carbon to oxygen atomic ratioin the novel metal alloy is generally about 2.5-5:1 (i.e., weight ratioof about 1.88-3.75:1). As can be appreciated, other atomic ratios of thecarbon to oxygen in the novel metal alloy can be used. The novel metalalloy includes a controlled amount of nitrogen. Large amounts ofnitrogen in the novel metal alloy can adversely affect the ductility ofthe novel metal alloy. This can in turn adversely affect the elongationproperties of the novel metal alloy. A nitrogen content in the novelmetal alloy of over 20 ppm can begin to cause the ductility of the novelmetal alloy to unacceptably decrease, thus adversely affect one or morephysical properties of the metal alloy that are useful or desired informing and/or using the medical device. In one non-limiting embodimentof the invention, the novel metal alloy includes less than about 30 ppmnitrogen. In one non-limiting formulation, the novel metal alloyincludes less than about 25 ppm nitrogen. In still another and/oralternative non-limiting formulation, the novel metal alloy includesless than about 10 ppm nitrogen. In yet another and/or alternativenon-limiting formulation, the novel metal alloy includes less than about5 ppm nitrogen. As can be appreciated, other amounts of nitrogen in thenovel metal alloy can exist. The novel metal alloy has several physicalproperties that positively affect the medical device when at leastpartially formed of the novel metal alloy. In one non-limitingembodiment of the invention, the average hardness of the novel metalalloy tube used to form the medical device is generally at least about60 (HRC) at 77° F. In one non-limiting aspect of this embodiment, theaverage hardness of the novel metal alloy tube used to form the medicaldevice is generally at least about 70 (HRC) at 77° F., and typicallyabout 80-100 (HRC) at 77° F. In another and/or alternative non-limitingembodiment of the invention, the average ultimate tensile strength ofthe novel metal alloy used to form the medical device is generally atleast about 60 UTS (ksi). In non-limiting aspect of this embodiment, theaverage ultimate tensile strength of the novel metal alloy used to formthe medical device is generally at least about 70 UTS (ksi), typicallyabout 80-150 UTS (ksi), and more typically about 100-150 UTS (ksi). Instill another and/or alternative non-limiting embodiment of theinvention, the average yield strength of the novel metal alloy used toform the medical device is at least about 70 ksi. In one non-limitingaspect of this embodiment, the average yield strength of the novel metalalloy used to form the medical device is at least about 80 ksi, andtypically about 100-140 (ksi). In yet another and/or alternativenon-limiting embodiment of the invention, the average grain size of thenovel metal alloy used to form the medical device is greater than 5 ASTM(e.g., ASTM E 112-96). The small grain size of the novel metal alloyenables the medical device to have the desired elongation and ductilityproperties that are useful in enabling the medical device to be formed,crimped and/or expanded. In one non-limiting aspect of this embodiment,the average grain size of the novel metal alloy used to form the medicaldevice is about 5.2-10 ASTM, typically about 5.5-9 ASTM, more typicallyabout 6-9 ASTM, still more typically about 6-8 ASTM, even more typicallyabout 6-7 ASTM, and still even more typically about 6.5-7 ASTM. In stillyet another and/or alternative non-limiting embodiment of the invention,the average tensile elongation of the novel metal alloy used to form themedical device is at least about 25%. An average tensile elongation ofat least 25% for the novel metal alloy is important to enable themedical device to be properly expanded when positioned in the treatmentarea of a body passageway. A medical device that does not have anaverage tensile elongation of at least about 25% can form micro-cracksand/or break during the forming, crimping and/or expansion of themedical device. In one non-limiting aspect of this embodiment, theaverage tensile elongation of the novel metal alloy used to form themedical device is about 25-35%. The unique combination of the rheniumcontent in the novel metal alloy in combination with achieving thedesired purity and composition of the alloy and the desired grain sizeof the novel metal alloy results in 1) a medical device having thedesired high ductility at about room temperature, 2) a medical devicehaving the desired amount of tensile elongation, 3) a homogeneous orsolid solution of a metal alloy having high radiopacity, 4) a reductionor prevention of microcrack formation and/or breaking of the metal alloytube when the metal alloy tube is sized and/or cut to form the medicaldevice, 5) a reduction or prevention of microcrack formation and/orbreaking of the medical device when the medical device is crimped onto aballoon and/or other type of medical device for insertion into a bodypassageway, 6) a reduction or prevention of microcrack formation and/orbreaking of the medical device when the medical device is bent and/orexpanded in a body passageway, 7) a medical device having the desiredultimate tensile strength and yield strength, 8) a medical device thatcan have very thin wall thicknesses and still have the desired radialforces needed to retain the body passageway on an open state when themedical device has been expanded, and/or 9) a medical device thatexhibits less recoil when the medical device is crimped onto a deliverysystem and/or expanded in a body passageway. Several non-limitingexamples of the novel metal alloy in accordance with the presentinvention are set forth below: Metal/ Wt. % Ex. 1 Ex. 2 C <150 ppm  <50ppm Mo 51-54% 52.5-55.5% O <50 ppm <10 ppm N <20 ppm <10 ppm Re 46-49%44.5-47.5% Metal/ Wt. % Ex. 3 Ex. 4 Ex. 5 Ex. 6 C ≦50 ppm ≦50 ppm ≦50ppm ≦50 ppm Mo 51-54% 52.5-55.5%   52-56% 52.5-55% O ≦20 ppm ≦20 ppm ≦10ppm ≦10 ppm N ≦20 ppm ≦20 ppm ≦10 ppm ≦10 ppm Re 46-49% 44.5-47.5%  44-48% 45-47.5% Ti   ≦0.4% ≦0.4% 0.2-0.4%   0.3-0.4% Y  ≦0.1% ≦0.1%0-0.08%  0.005-0.05%   Zr  ≦0.2% ≦0.2%  0-0.2% 0.1-0.25%  Metal/ Wt. %Ex. 7 Ex. 8 Ex. 9 Ex. 10 C ≦40 ppm ≦40 ppm ≦40 ppm ≦40 ppm Mo 51-53%51.5-54% 52-55% 52.5-55% O ≦15 ppm ≦15 ppm ≦15 ppm ≦10 ppm N ≦10 ppm ≦10ppm ≦10 ppm ≦10 ppm Re 47-49% 46-48.5% 45-48% 45-47.5% Ti 0.1-0.35%    0%   0%  0.1-0.3% Y   0% 0.002-0.08%     0%    0% Zr   0%    0%00.1-0.2%  0.05-0.15%  Metal/ Wt. % Ex. 11 Ex. 12 C ≦40 ppm ≦40 ppm Mo52-55% 52.5-55.5% O ≦10 ppm ≦10 ppm N ≦10 ppm ≦10 ppm Re 45-49%44.5-47.5% Ti 0.05-0.4%      0% Y 0.005-0.07%   0.004-0.06%  Zr   0% 0.1-0.2%

In examples 1 and 2 above, the novel metal alloy is principally formedof rhenium and molybdenum and the content of other metals and/orimpurities is less than about 0.1 weight percent of the novel metalalloy, the atomic ratio of carbon to oxygen is about 2.5-10:1 (i.e.,weight ratio of about 1.88-7.5:1), the average grain size of the novelmetal alloy is about 6-9 ASTM, the tensile elongation of the metal alloyis about 25-35%, the average density of the metal alloy is at leastabout 13.4 gm/cc, the average yield strength of the metal alloy is about98-122 (ksi), the average ultimate tensile strength of the metal alloyis about 100-150 UTS (ksi), and the average hardness of the metal alloyis about 80-100 (HRC) at 77° F. In examples 3-12 above, the novel metalalloy is principally formed of rhenium and molybdenum and at least onemetal of titanium, yttrium and/or zirconium, and the content of othermetals and/or impurities is less than about 0.1 weight percent of thenovel metal alloy, the ratio of carbon to oxygen is about 2.5-10:1, theaverage grain size of the novel metal alloy is about 6-9 ASTM, thetensile elongation of the metal alloy is about 25-35%, the averagedensity of the metal alloy is at least about 13.6 gm/cc, the averageyield strength of the metal alloy is at least about 110 (ksi), theaverage ultimate tensile strength of the metal alloy is about 100-150UTS (ksi), and the average hardness of the metal alloy is about 80-100(HRC) at 77° F.

In still a further and/or alternative one non-limiting aspect of theinvention, the novel metal alloy that is used to form all or a portionof the medical device includes tantalum and tungsten. In onenon-limiting embodiment, the novel metal alloy is formed of a majorityweight percent tantalum and tungsten. Typically, the tantalum andtungsten content of the novel metal alloy is at least about 80 weightpercent, more typically at least about 90 weight percent, even moretypically at least about 95 weight percent, still even more typically atleast about 99 weight percent, and yet even more typically at leastabout 99.9 weight percent; however, other weight percentages can beused. Generally the novel metal alloy of tantalum and tungsten includesat least about 0.5 weight percent tungsten and at least about 10 weightpercent tantalum, typically at least about 2 weight percent tungsten andat least about 20 weight percent tantalum, and more typically at leastabout 2.5 weight percent tungsten and at least about 50 weight percenttantalum; however, other weight percentages of the tantalum and/ortungsten in the novel metal alloy can be used. Generally the novel metalalloy of tantalum and tungsten includes less than about 2 weight percentimpurities, typically less than about 1 weight percent impurities, moretypically less than about 0.5 weight percent impurities, still moretypically less than about 0.1 weight percent impurities, yet moretypically less than about 0.03 weight percent impurities; however, otherweight percent of impurities in the novel metal alloy can be used. Theweight percent of carbon in the alloy of tantalum and tungsten isgenerally less than about 100 ppm, and typically less than about 50 ppm,more typically less than about 40 ppm, and still more typically lessthan about 25 ppm; however, other weight percentages of carbon in thenovel metal alloy can be used. The weight percent of oxygen in the alloyof tantalum and tungsten is generally less than about 100 ppm, andtypically less than about 50 ppm, more typically less than about 40 ppm,and still more typically less than about 25 ppm; however, other weightpercentages of oxygen in the novel metal alloy can be used. The weightpercent of nitrogen in the alloy of tantalum and tungsten is generallyless than about 50 ppm, and typically less than about 40 ppm, moretypically less than about 30 ppm, and still more typically less thanabout 25 ppm; however, other weight percentages of nitrogen in the novelmetal alloy can be used. Several specific non-limiting novel metal alloycompositions for the tantalum and tungsten alloy that can form a part ofor the complete medical device are set forth below in weight percent orppm: Metal/ Wt. % Ex. 1 Ex. 2 Ex. 3 C 0-50 ppm 0-50 ppm 0-50 ppm Ca 0-1% 0-0.5% 0% Mg  0%  0-3% 0% Mo  0%  0-2% 0% O 0-50 ppm 0-50 ppm 0-50 ppmN 0-50 ppm 0-50 ppm 0-50 ppm Rare Earth 0-1%  0-0.5% 0% Metal Ta 85-96% 10-90% 85-95%   W 4-15%  10-90% 5-15%   Metal/ Wt. % Ex. 4 Ex. 5 Ex. 6 C0-50 ppm 0-50 ppm 0-50 ppm Ca 0% 0% 0% Mg 0% 0% 0% Mo 0% 0% 0% O 0-50ppm 0-50 ppm 0-50 ppm N 0-50 ppm 0-50 ppm 0-50 ppm Rare Earth 0% 0% 0%Metal Ta 90.5-98%    95-98%   90-97.5%    W 2-9.5%   2% to less2.5-10%    than 5%

The impurity content in each of these examples is less than about 0.04weight percent.

In still a further and/or alternative one non-limiting aspect of theinvention, the novel metal alloy that is used to form all or a portionof the medical device increases the strength of the medical device ascompared with stainless steel or chromium-cobalt alloys, thus lessquantity of novel metal alloy can be used in the medical device toachieve similar strengths as compared to medical devices formed ofdifferent metals. As such, the resulting medical device can be madesmaller and less bulky by use of the novel metal alloy withoutsacrificing the strength and durability of the medical device. Such amedical device can have a smaller profile, thus can be inserted insmaller areas, openings and/or passageways. The novel metal alloy alsocan increase the radial strength of the medical device. For instance,the thickness of the walls of the medical device and/or the wires usedto form the medical device can be made thinner and achieve a similar orimproved radial strength as compared with thicker walled medical devicesformed of stainless steel or cobalt and chromium alloy. The novel metalalloy also can improve stress-strain properties, bendability andflexibility of the medical device, thus increase the life of the medicaldevice. For instance, the medical device can be used in regions thatsubject the medical device to bending. Due to the improved physicalproperties of the medical device from the novel metal alloy, the medicaldevice has improved resistance to fracturing in such frequent bendingenvironments. In addition or alternatively, the improved bendability andflexibility of the medical device due to the use of the novel metalalloy can enable the medical device to be more easily inserted into abody passageway. The novel metal alloy can also reduce the degree ofrecoil during the crimping and/or expansion of the medical device. Forexample, the medical device better maintains its crimped form and/orbetter maintains its expanded form after expansion due to the use of thenovel metal alloy. As such, when the medical device is to be mountedonto a delivery device when the medical device is crimped, the medicaldevice better maintains its smaller profile during the insertion of themedical device in a body passageway. Also, the medical device bettermaintains its expanded profile after expansion so as to facilitate inthe success of the medical device in the treatment area. In addition tothe improved physical properties of the medical device by use of thenovel metal alloy, the novel metal alloy has improved radiopaqueproperties as compared to standard materials such as stainless steel orcobalt-chromium alloy, thus reducing or eliminating the need for usingmarker materials on the medical device. For instance, the novel metalalloy is at least about 10-20% more radiopaque than stainless steel orcobalt-chromium alloy. The medical device that is at least partiallyformed from the novel metal alloy can be form by a variety ofmanufacturing techniques. In one non-limiting embodiment of theinvention, the medical device that is at least partially formed from arod or tube of the novel metal alloy. Medical devices that can be formedfrom a rod or tube include, but are not limited to, stents, grafts,vascular grafts, valves, orthopedic implants, sheaths, guide wires,balloon catheters, hypotubes, catheters, electrophysiology catheters,cutting devices, etc.

In another and/or alternative non-limiting aspect of the invention, themedical device can include a bistable construction. In such a design,the medical device has two or more stable configurations, including afirst stable configuration with a first cross-sectional shape and asecond stable configuration with a second cross-sectional shape. All ora portion of the medical device can include the bistable construction.The bistable construction can result in a generally uniform change inshape of the medical device, or one portion of the medical device canchange into one or more configurations and one or more other portions ofthe medical device can change into one or more other configurations.

In still another and/or alternative non-limiting aspect of theinvention, the medical device can be used in conjunction with one ormore other biological agents that are not on the medical device. Forinstance, the success of the medical device can be improved by infusing,injecting or consuming orally one or more biological agents. Suchbiological agents can be the same and/or different from the one or morebiological agents on and/or in the medical device. Such use of one ormore biological agents are commonly used in systemic treatment of apatient after a medical procedure such as body wide aggressiveanti-platelet and/or anti-coagulation therapy after the medical devicehas been inserted in the treatment area can be reduced or eliminated byuse of the novel alloy. Although the medical device of the presentinvention can be designed to reduce or eliminate the need for longperiods of body wide aggressive anti-platelet and/or anti-coagulationtherapy after the medical device has been inserted in the treatmentarea, the use of one or more biological agents can be used inconjunction with the medical device to enhance the success of themedical device and/or reduce or prevent the occurrence of thrombosis.For instance, solid dosage forms of biological agents for oraladministration, and/or for other types of administration (e.g.,suppositories, etc.) can be used. Such solid forms can include, but arenot limited to, capsules, tablets, effervescent tablets, chewabletablets, pills, powders, sachets, granules and gels. The solid form ofthe capsules, tablets, effervescent tablets, chewable tablets, pills,etc. can have a variety of shapes such as, but not limited to,spherical, cubical, cylindrical, pyramidal, and the like. In such soliddosage form, one or more biological agents can be admixed with at leastone filler material such as, but not limited to, sucrose, lactose orstarch; however, this is not required. Such dosage forms can includeadditional substances such as, but not limited to, inert diluents (e.g.,lubricating agents, etc.). When capsules, tablets, effervescent tabletsor pills are used, the dosage form can also include buffering agents;however, this is not required. Soft gelatin capsules can be prepared tocontain a mixture of the one or more biological agents in combinationwith vegetable oil or other types of oil; however, this is not required.Hard gelatin capsules can contain granules of the one or more biologicalagents in combination with a solid carrier such as, but not limited to,lactose, potato starch, corn starch, cellulose derivatives of gelatin,etc; however, this is not required. Tablets and pills can be preparedwith enteric coatings for additional time release characteristics;however, this is not required. Liquid dosage forms of the one or morebiological agents for oral administration can include pharmaceuticallyacceptable emulsions, solutions, suspensions, syrups, elixirs, etc.;however, this is not required. In one non-limiting embodiment, when atleast a portion of one or more biological agents is inserted into atreatment area (e.g., gel form, paste form, etc.) and/or provided orally(e.g., pill, capsule, etc.) and/or anally (suppository, etc.), one ormore of the biological agents can be controllably released; however,this is not required. In one non-limiting example, one or morebiological agents can be given to a patient in solid dosage form and oneor more of such biological agents can be controllably released from suchsolid dosage forms. In another and/or alternative non-limiting exampletrapidil, trapidil derivatives, taxol, taxol derivatives, cytochalasin,cytochalasin derivatives, paclitaxel, paclitaxel derivatives, rapamycin,rapamycin derivatives, 5-Phenylmethimazole, 5-Phenylmethimazolederivatives, GM-CSF, GM-CSF derivatives, or combinations thereof aregiven to a patient prior to, during and/or after the insertion of themedical device in a treatment area. Certain types of biological agentsmay be desirable to be present in a treated area for an extended periodof time in order to utilize the full or nearly full clinical potentialthe biological agent. For instance, trapidil and/or trapidil derivativesis a compound that has many clinical attributes including, but notlimited to, anti-platelet effects, inhibition of smooth muscle cells andmonocytes, fibroblast proliferation and increased MAPK-1 which in turndeactivates kinase, a vasodilator, etc. These attributes can beeffective in improving the success of a medical device that has beeninserted at a treatment area. In some situations, these positive effectsof trapidil and/or trapidil derivatives need to be prolonged in atreatment area in order to achieve complete clinical competency.Trapidil and/or trapidil derivatives has a half life in vivo of about2-4 hours with hepatic clearance of 48 hours. In order to utilize thefull clinical potential of trapidil and/or trapidil derivatives,trapidil and/or trapidil derivatives should be metabolized over anextended period of time without interruption; however, this is notrequired. By inserting trapidil and/or trapidil derivatives in a soliddosage form, the trapidil and/or trapidil derivatives could be releasedin a patient over extended periods of time in a controlled manner toachieve complete or nearly complete clinical competency of the trapidiland/or trapidil derivatives. In another and/or alternative non-limitingexample, one or more biological agents are at least partiallyencapsulated in one or more polymers. The one or more polymers can bebiodegradable, non-biodegradable, porous, and/or non-porous. When theone or more polymers are biodegradable, the rate of degradation of theone or more biodegradable polymers can be used to at least partiallycontrol the rate at which one or more biological agent are released intoa body passageway and/or other parts of the body over time. The one ormore biological agents can be at least partially encapsulated withdifferent polymer coating thickness, different numbers of coatinglayers, and/or with different polymers to alter the rate at which one ormore biological agents are released in a body passageway and/or otherparts of the body over time. The rate of degradation of the polymer isprincipally a function of 1) the water permeability and solubility ofthe polymer, 2) chemical composition of the polymer and/or biologicalagent, 3) mechanism of hydrolysis of the polymer, 4) the biologicalagent encapsulated in the polymer, 5) the size, shape and surface volumeof the polymer, 6) porosity of the polymer, 7) the molecular weight ofthe polymer, 8) the degree of cross-linking in the polymer, 9) thedegree of chemical bonding between the polymer and biological agent,and/or 10) the structure of the polymer and/or biological agent. As canbe appreciated, other factors may also affect the rate of degradation ofthe polymer. When the one or more polymers are biostable, the rate atwhen the one or more biological agents are released from the biostablepolymer is a function of 1) the porosity of the polymer, 2) themolecular diffusion rate of the biological agent through the polymer, 3)the degree of cross-linking in the polymer, 4) the degree of chemicalbonding between the polymer and biological agent, 5) chemicalcomposition of the polymer and/or biological agent, 6) the biologicalagent encapsulated in the polymer, 7) the size, shape and surface volumeof the polymer, and/or 8) the structure of the polymer and/or biologicalagent. As can be appreciated, other factors may also affect the rate ofrelease of the one or more biological agents from the biostable polymer.Many different polymers can be used such as, but not limited to,aliphatic polyester compounds (e.g., PLA (i.e. poly(D, L-lactic acid),poly(L-lactic acid)), PLGA (i.e. poly(lactide-co-glycoside), etc.), POE,PEG, PLLA, parylene, chitosan and/or derivatives thereof. As can beappreciated, the at least partially encapsulated biological agent can beintroduced into a patient by means other than by oral introduction, suchas, but not limited to, injection, topical applications, intravenously,eye drops, nasal spray, surgical insertion, suppositories,intrarticularly, intraocularly, intranasally, intradermally,sublingually, intravesically, intrathecally, intraperitoneally,intracranially, intramuscularly, subcutaneously, directly at aparticular site, and the like.

In yet another and/or alternative non-limiting aspect of the invention,the medical device is in the form of a stent. The stent can be anexpandable stent that is expandable by a balloon and/or isself-expanding. The stent can have one or more body members. The one ormore body members can include first and second ends and a wall surfacedisposed between the first and second ends. Typically each body memberhas a first cross-sectional area which permits delivery of the bodymember into a body passageway, and a second, expanded cross-sectionalarea. The expansion of one or more body members of the stent can beaccomplished in a variety of manners. In one manner, one or more bodymembers are expanded to the second cross-sectional area by a radially,outwardly extending force applied at least partially from the interiorregion of the body member (e.g. by use of a balloon, etc.). The bodymember can include shape memory materials; however, this is notrequired. The second cross-sectional area of the stent can be fixed orvariable. The stent can be designed such that one or more body membersexpand while substantially retaining the original longitudinal length ofthe body member; however, this is not required. The one or more bodymembers can have a first cross-sectional shape that is generallycircular so as to form a substantially tubular body member; however, theone or more body members can have other cross-sectional shapes. When thestent includes two or more body members, the two or more body memberscan be connected together by at least one connector member. The stentcan include rounded, smooth and/or blunt surfaces to minimize and/orprevent potential damage to a body passageway as the stent is insertedinto a body passageway and/or expanded in a body passageway; however,this is not required. The stent can be treated with gamma, beta and/ore-beam radiation, and/or otherwise sterilized; however, this is notrequired.

In one non-limiting application of the present invention, there isprovided a medical device and method for using such medical device toinhibit or prevent thrombosis after the medical device has been insertedinto a body passageway. The medical device can have one-limitingadvantage of reducing or eliminating the need for long periods ofbody-wide anti-platelet and/or anti-coagulation therapy after themedical device has been inserted in the treatment area. The medicaldevice can have one non-limiting advantage of delivering one or morebiological agents into a treatment area (e.g., body passageway, etc.).Such a medical device can be designed to be inserted in and/or beconnected to a body passageway (e.g., blood vessel, etc.) and whichmedical device inhibits or prevents thrombosis. The medical device canbe designed to be used as a biological agent delivery mechanism todeliver one or more biological agents to and/or into a wall of a bodypassageway and/or down stream from the site of implantation of themedical device. In one non-limiting design, the medical device is astent comprised of a base material that includes at least one layer ofbiological agent and at least one polymer layer that is used to atpartially control the release of the biological agent from the medicaldevice. In one non-limiting controlled release arrangement, moleculardiffusion through a polymer is used to control the release rate of oneor more biological agents from the medical device When a moleculardiffusion mechanism is used, one or more non-porous polymer layers canbe used to facilitate in such molecular diffusion; however, this is notrequired. The molecular composition, molecular structure and/or coatingthickness of the non-porous polymer can be selected to control therelease rate of one or more biological agents from the medical device.In another and/or alternative non-limiting design, the medical device isa surgical graft comprised of a flexible base material upon which atleast one layer of at least one biological agent is applied to an innerand/or outer surface of the surgical graft. At least one polymer layercan be applied to the surgical graft to at least partially control therelease rate of the one or more biological agents from the surgicalgraft; however, this is not required. The polymer layer can include aporous or non-porous polymer. The one or more polymers and/or biologicalagents that are used in conjunction with the stent or the surgical graftcan 1) form at least a portion of the medical device, 2) be coated onone or more regions of the medical device, and/or 3) be contained in oneor more regions within the medical device. Non-limiting examples ofpolymers that can be used include parylene, PLGA, POE, PGA, PLLA, PAA,PEG, chitosan and/or derivatives of one or more of these polymers;however, other or additional polymers can be used. Many differentbiological agents can be used. Such biological agents can includeanti-platelet compounds and/or anticoagulant compounds such as, but notlimited to, warfarin (Coumadin) and/or derivatives, aspirin and/orderivatives, clopidogrel and/or derivatives, ticlopadine and/orderivatives, hirdun and/or derivatives, dipyridamole and/or derivatives,trapidil and/or derivatives, and/or heparin and/or low molecular weightheparin and/or derivatives. As can be appreciated, one or more otheranti-thrombotic biological agents can be combined with the medicaldevice such as, but not limited to, taxol, taxol derivatives,cytochalasin, cytochalasin derivatives, paclitaxel, paclitaxelderivatives, rapamycin, rapamycin derivatives, 5-Phenylmethimazole,5-Phenylmethimazole derivatives, GM-CSF, GM-CSF derivatives, orcombinations thereof. The structure of the medical device duringmanufacture can be pre-treated (e.g., plasma etching, etc.) tofacilitate in the coating of one or more polymers and/or biologicalagents on the medical device; however, this is not required. The surfacetopography of the base structure of the medical device can be uniform orvaried to achieve the desired operation and/or biological agent releasedfrom the medical device. As can be appreciated, one or more regions ofthe medical device can be constructed by use of one or moremicroelectromechanical manufacturing techniques; however, this is notrequired. Materials that can be used by microelectromechanicalmanufacturing techniques technology include, but are not limited to,chitosan, a chitosan derivative, PLGA, a PLGA derivative, PLA, a PLAderivative, PEVA, a PEVA derivative, PBMA, a PBMA derivative, POE, a POEderivative, PGA, a PGA derivative, PLLA, a PLLA derivative, PAA, a PAAderivative, PEG, and chitosan, a chitosan derivative, PLGA, a PLGAderivative, PLA, a PLA derivative, PEVA, a PEVA derivative, PBMA, a PBMAderivative, POE, a POE derivative, PGA, a PGA derivative, PLLA, a PLLAderivative, PAA, a PAA derivative, PEG, a PEG derivative, and/or a PEGderivative. The medical device can include one or more surfacestructures, micro-structures, internal structures that include one ormore biological agents and/or polymers; however, this is not required.These structures can be at least partially formed by MEMS (e.g.,micro-machining, etc.) technology and/or other types of technology. Thestructures can be designed to contain and/or be fluidly connected to apassageway in the medical device that includes one or more biologicalagents; however, this is not required. The structures can be used toengage and/or penetrate surrounding tissue or organs once the medicaldevice has been positioned on and/or in a patient; however, this is notrequired. One or more polymers and/or biological agents can be insertedin these structures and/or at least partially form these structures ofthe medical device. The structures can be clustered together ordisbursed throughout the surface of the medical device. Similar shapedand/or sized structures can be used, or different shaped and/or sizedstructures can be used. Typically the micro-structures, when formed,extend from or into the outer surface no more than about 400 microns,and more typically less than about 300 microns, and more typically about15-250 microns; however, other sizes can be used. The time period one ormore biological agents are released from the medical device is typicallydependent on the designed medical treatment and/or other factors. In onenon-limiting arrangement, one or more biological agents are releasedfrom the medical device for at least several days after the medicaldevice is inserted in the body of a patient; however, this is notrequired. In another one non-limiting arrangement, one or morebiological agents are released from the medical device for at leastabout one week after the medical device is inserted in the body of apatient. In still another one non-limiting arrangement, one or morebiological agents are released from the medical device for at leastabout two weeks after the medical device is inserted in the body of apatient. In yet another one non-limiting arrangement, one or morebiological agents are released from the medical device for about oneweek to one year after the medical device is inserted in the body of apatient. As can be appreciated, the time frame that one or more of thebiological agents can be released from the medical device can be longeror shorter. The time period for the release of two or more biologicalagents from the medical device can be the same or different. The type ofthe one or more biological agents used on the medical device, therelease rate of the one or more biological agents from the medicaldevice, and/or the concentration of the one or more biological agentsbeing released from the medical device can be the same or different. Thecontrolled release rate of one or more biological agents from themedical device can result in reduced amounts and/or reduce time periodof systemic drug therapy after the medical device is inserted in thetreatment area. In one non-limiting arrangement, the medical devicereleases one or more biological agents for a period of time such thatsystemic drug therapy after the medical device is inserted in thetreatment area is reduced to less than one year. In another and/oralternative non-limiting arrangement, the medical device releases one ormore biological agents for a period of time such that systemic drugtherapy after the medical device is inserted in the treatment area isreduced to less than one month. In still another and/or alternativenon-limiting arrangement, the medical device releases one or morebiological agents for a period of time such that systemic drug therapyafter the medical device is inserted in the treatment area is reduced toless than one week. The medical device can be temporality used inconjunction with other biological agents. For instance, the success ofthe medical device can be improved by infusing, injecting or consumingorally one or more biological agents. Such biological agents can be thesame and/or different from the one or more biological agents on and/orin the medical device. For instance, solid dosage forms of biologicalagents for oral administration can be used. Such solid forms caninclude, but are not limited to, capsules, tablets, effervescenttablets, chewable tablets, pills, powders, sachets, granules and gels.

In another and/or alternative non-limiting application of the presentinvention, there is provided a medical device that is adapted forintroduction into a patient and/or for topical use (e.g., lotion, salve,gel, etc.), which medical device releases one or more biological agentsin a controlled release manner. The medical device can have a variety ofapplications such as, but not limited to, placement into the vascularsystem. As can be appreciated, the medical device can have other oradditional uses. One or more biological agents on and/or in the medicaldevice can be released controllably and/or uncontrollably from themedical device. As such, all of the biological agents can becontrollably released from the medical device, all of the biologicalagents can be uncontrollably released from the medical device, or one ormore biological agents can be controllably released and one or morebiological agents can be uncontrollably released from the medicaldevice. The controlled release of the one or more biological agents fromthe medical device can be at least partially controlled by moleculardiffusion through one or more non-porous polymer layers; however, itwill be appreciated that other or additional mechanisms can be used tocontrol the rate of release of one or more biological agents from themedical device. For instance, the one or more biological agents can beselected so as to be chemically bonded to one or more polymers tocontrol the rate of release of one or more biological agents from themedical device; however, this is not required. The one or more polymerscan include cross-links to control the rate of release of one or morebiological agents from the medical device; however, this is notrequired. The one or more polymers and/or one or more biological agentscan be hydrophobic or hydrophilic, thus can be used to facilitate in thecontrolled release of the one or more biological agents from the medicaldevice; however, this is not required. The thickness of the one or morepolymer layers can be selected to facilitate in the controlled releaseof the one or more biological agents; however, this is not required. Themolecular weight and/or molecular structure of the one or morebiological agents and/or one or more polymer can be selected tofacilitate in the release of the one or more biological agents; however,this is not required. Many different biological agents can be used. Suchbiological agents can include anti-platelet compounds and/oranticoagulant compounds such as, but not limited to, warfarin (Coumadin)and/or derivatives, aspirin and/or derivatives, clopidogrel and/orderivatives, ticlopadine and/or derivatives, hirdun and/or derivatives,dipyridamole and/or derivatives, trapidil and/or derivatives, and/orheparin and/or low molecular weight heparin and/or derivatives. As canbe appreciated, one or more other anti-thrombotic biological agents canbe combined with the medical device such as, but not limited to, taxol,taxol derivatives, cytochalasin, cytochalasin derivatives, paclitaxel,paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF, GM-CSFderivatives, or combinations thereof. In still another one non-limitingarrangement, one or more biological agents are released from the medicaldevice for at least about two weeks after the medical device is insertedin the body of a patient. In yet another one non-limiting arrangement,one or more biological agents are released from the medical device forabout one week to one year after the medical device is inserted in thebody of a patient. As can be appreciated, the time frame that one ormore of the biological agents can be released from the medical devicecan be longer or shorter. The time period for the release of two or morebiological agents from the medical device can be the same or different.The type of the one or more biological agents used on the medicaldevice, the release rate of the one or more biological agents from themedical device, and/or the concentration of the one or more biologicalagents being released from the medical device can be the same ordifferent.

One non-limiting object of the present invention is the provision of amedical device having improved procedural success rates.

Another and/or alternative non-limiting object of the present inventionis the provision of a medical device that can be implanted into thevascular system of a mammalian without the need of body wide aggressiveanti-platelet and/or anti-coagulation therapy over extended periods oftime and a method using such a device.

Still another and/or alternative non-limiting object of the presentinvention is the provision of a medical device in the form of a stentthat inhibits or prevents the occurrence of thrombosis after the medicaldevice has been inserted into a body passageway.

Yet another and/or alternative non-limiting object of the presentinvention is the provision of a medical device that is at leastpartially formed of, contains and/or is coated with one or morebiological agents.

Still yet another and/or alternative non-limiting object of the presentinvention is the provision of a medical device that inhibits or preventsthrombosis by localized release of one or more biological agents and amethod using such a device.

Another and/or alternative non-limiting object of the present inventionis the provision of a medical device that controllably releases one ormore biological agents.

Yet another and/or alternative non-limiting object of the presentinvention is the provision of a medical device that inhibits or preventsthe occurrence of in-stent restenosis, vascular narrowing and/orrestenosis after the medical device has been inserted into a bodypassageway.

Still another and/or alternative non-limiting object of the presentinvention is the provision of a medical device that includes one or moresurface structures and/or micro-structures.

Yet another and/or alternative non-limiting object of the presentinvention is the provision of a medical device that includes one or moreinternal structures, micro-structures and/or surface structures thatinclude and/or are coated with one or more biological agents and/orpolymers.

Still another and/or alternative non-limiting object of the presentinvention is the provision of a medical device that includes one or moresurface structures, micro-structures and/or internal structures and aprotective coating that at least partially covers and/or protects suchstructures.

Still a further and/or alternative non-limiting object of the presentinvention is the provision of a medical device that can be used inconjunction with one or more biological agents not on or in the medicaldevice.

These and other advantages will become apparent to those skilled in theart upon the reading and following of this description taken togetherwith the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

Reference may now be made to the drawings, which illustrate variousembodiments that the invention may take in physical form and in certainparts and arrangements of parts wherein:

FIG. 1 is a perspective view of a section of a medical device in theform of an unexpanded stent which permits delivery of the stent into abody passageway;

FIG. 2 is a sectional view of the stent of FIG. 1;

FIG. 3 is a cross-sectional view along line 3-3 of FIG. 2 illustratingone type of coating on a medical device;

FIG. 4 is a cross-sectional view along line 3-3 of FIG. 2 illustratinganother type of coating on a medical device;

FIG. 5 is a cross-sectional view along line 3-3 of FIG. 2 illustratinganother type of coating on a medical device;

FIG. 6 is a cross-sectional view along line 3-3 of FIG. 2 illustratinganother type of coating on a medical device;

FIG. 7 is a cross-sectional view along line 3-3 of FIG. 2 illustratingpores in the body of the medical device containing a biological agentand a coating on the medical device;

FIG. 8 is a cross-sectional view along line 3-3 of FIG. 2 illustratingpores in the body of the medical device containing a biological agentand a biological agent coating on the medical device;

FIG. 9 is a cross-sectional view along line 3-3 of FIG. 2 illustratingpores in the body of the medical device containing a biological agentand a biological agent coating on the medical device and a polymercoating over the biological agent;

FIG. 10 is a cross-sectional view along line 3-3 of FIG. 2 illustratingmicro-needles on the surface of the medical device that are formed of abiological agent;

FIG. 11 is a cross-sectional view along line 3-3 of FIG. 2 illustratingmicro-needles on the surface of the medical device that are formed of abiological agent and polymer;

FIG. 12 is a cross-sectional view along line 3-3 of FIG. 2 illustratingmicro-needles on the surface of the medical device that are formed of abiological agent and coated with a polymer;

FIG. 13 is a cross-sectional view along line 3-3 of FIG. 2 illustratingmicro-needles on the surface of the medical device that are formed of abiological agent and polymer and coated with a polymer;

FIG. 14 is a cross-sectional view along line 3-3 of FIG. 2 illustratingmicro-needles on the surface of the medical device that are formed of apolymer and includes an internal cavity that includes a biologicalagent;

FIG. 15 is a perspective view of a section of medical device in the formof a surgical graft that includes an internal biological agent coatingand a polymer coating over the biological agent;

FIG. 16 is an expanded section of the surgical graft identified in FIG.15; and,

FIG. 17 is a cross-sectional view of a micro-needle on a medical devicethat is penetrating into the inner surface of a body passageway ororgan.

DETAILED DESCRIPTION OF THE INVENTION

Referring now to the drawings wherein the showing is for the purpose ofillustrating preferred embodiments of the invention only and not for thepurpose of limiting the same, FIGS. 1-2 disclose a medical device in theform of a stent for use in a body passageway. The medical device of thepresent invention can be designed to address one or more of theshortcomings of prior medical devices. One non-limiting feature of themedical device of the present invention can be to locally deliver one ormore biological agents to a particular body region. Another and/oralternative non-limiting feature of the medical device of the presentinvention can be to locally deliver one or more biological agents to aparticular body region and to at least partially release one or morebiological agents in a controlled manner.

Although, FIGS. 1-2 illustrate the medical device in the form of a stentfor use in the cardiovascular field, the medical device can be used inother medical fields such as, but not limited to, orthopedic field,cardiology field, pulmonology field, urology field, nephrology field,gastrointerology field, gynecology field, otolaryngology field or othersurgical fields. The medical device can be in a form other than a stentsuch as a surgical graft as illustrated in FIGS. 15 & 16), a suture, astaple, an orthopedic implant, a bandage, a valve, a micro or nanodevice, a vascular implant, a drug delivery catheter, an infusioncatheter, a balloon, a catheter tip, a drug pump, tubing, a bag, a lead,a pacemaker, an implantable pulse generator, an implantable cardiacdefibrillator, a cardio-verger defibrillator, a defibrillator, a spinalstimulator, a brain stimulator, a sacral nerve stimulator, a chemicalsensor, a spinal implant, a membrane surface, a sheath, a guide wire, aballoon catheter, a hypotube, a catheter (e.g., electrophysiologycatheters, guide catheter, stent catheter, etc.), a cutting device, aPFO (patent foramen ovale) device, a wrap, a biological glue, a gel,etc. As can be appreciated, the medical device can take other forms(e.g., lotions, salves, gels, capsules, tablets, effervescent tablets,chewable tablets, pills, powders, sachets, granules, etc.).

The medical device of the present invention, when used for vascularapplications, can be used to address various medical problems such as,but not limited to, restenosis, atherosclerosis, atherogenesis, angina,ischemic disease, congestive heart failure or pulmonary edema associatedwith acute myocardial infarction, atherosclerosis, thrombosis,controlling blood pressure in hypertension, platelet adhesion, plateletaggregation, smooth muscle cell proliferation, vascular complications,wounds, myocardial infarction, pulmonary thromboembolism, cerebralthromboembolism, thrombophiebitis, thrombocytopenia or bleedingdisorders.

The medical device can be formed of a variety of materials such as, butnot limited to, biostable polymers, biodegradable polymers, metals,plastics, cloth, fibers, or any combination thereof. As can beappreciated, many types of biodegradable polymers and non-biodegradablepolymers can be used to at least partially form the medical device. Themedical device can be at least partially biostable or at least partiallybiodegradable. The material or materials used to form the medical deviceinclude properties (e.g., strength, durability, hardness, biostability,bendability, coefficient of friction, radial strength, flexibility,tensile strength, longitudinal lengthening, stress-strain properties,improved recoil properties, radiopacity, heat sensitivity,biocompatability, biostability, biodegradability, biocompatability,etc.) that are selected to form a medical device which promotes thesuccess of the medical device. When the medical device is in the form ofa stent, the stent can be expandable such as by a balloon and/or selfexpanding. The material that is used to form one or more portions of themedical device is typically selected to withstand the manufacturingprocess used to form the medical device (e.g., electroplating, electropolishing, extrusion, molding, EDM machining, MEMS (e.g.,micro-machining, etc.) manufacturing, chemical polishing, ion beamdeposition or implantation, sputter coating, vacuum deposition, plasmadeposition, etc.).

The medical device can include one or more surface structures,micro-structures and/or internal structures. Such structures can beformed by a variety of processes (e.g., machining, chemicalmodifications, chemical reactions, micro-machining, etching, etc.). Theone or more coatings and/or one or more surface structures,micro-structures and/or internal structures of the medical device can beused for a variety of purposes such as, but not limited to, 1)increasing the bonding and/or adhesion of one or more biological agents,adhesives, marker materials and/or polymers to the medical device, 2)changing the appearance or surface characteristics of the medicaldevice, and/or 3) controlling the release rate of one or more biologicalagents. The techniques employed to deliver the medical device include,but are not limited to, angioplasty, vascular anastomoses,transplantation, implantation, subcutaneous introduction, minimallyinvasive surgical procedures, injection, topical applications, bolusadministration, infusion, interventional procedures, and anycombinations thereof. When the medical device is in the form of asurgical graft or stent as illustrated in FIGS. 1-17, the medical devicecan be implanted or applied by techniques such as, but not limited to,suturing, staples, adhesive, anastomoses, balloon delivery, sheathcatheter delivery, etc.

Referring again to FIGS. 1-2, there is disclosed a medical device in theform of a stent for a body passageway. The stent is an expandable stentfor at least partially expanding occluded segments of a body passageway;however, the stent can have other or additional uses. For example, theexpandable stent may be used for, but not limited to, such purposesas 1) a supportive stent for placement within a blocked vasculatureopened by transluminal recanalization, which are likely to collapse inthe absence of an internal support; 2) forming a catheter passagethrough the mediastinal and/or other veins occluded by inoperablecancers; 3) reinforcement of catheter created intrahepaticcommunications between portal and/or hepatic veins in patients sufferingfrom portal hypertension; 4) a supportive stent for placement in thenarrowing of the esophagus, the intestine, the ureter and/or theurethra; and/or 5) a supportive stent for reinforcement of reopenedand/or previously obstructed bile ducts. Accordingly, use of the term“stent” encompasses the foregoing or other usages within various typesof body passageways.

As illustrated in FIG. 1, the medical device 20 in the form of anexpandable stent includes at least one tubular shaped body member 30having a first end 32, a second end 34, and member structures 36disposed between the first and second ends. FIG. 2 illustrates the stentprior to being formed into a generally tubular shape. As can beappreciated, the stent can be formed of a plurality of body membersconnected together. Body member 30 has a first diameter which permitsdelivery of the body member into a body passageway. The first diameterof the body member is illustrated as being substantially constant alongthe longitudinal length of the body member. As can be appreciated, thebody member can have a varying first diameter along at least a portionof the longitudinal length of the body member. The body member also hasa second expanded diameter, not shown. The second diameter typicallyvaries in size; however, the second diameter can be non-variable insize. The stent can be expanded in a variety of ways such as by aballoon and/or be at least partially self expanding. A balloonexpandable stent is typically pre-mounted or crimped onto an angioplastyballoon catheter. The balloon catheter is then positioned into thepatient via a guide wire. Once the stent is properly positioned, theballoon catheter is inflated to the appropriate pressure for stentexpansion. After the stent has been expanded, the balloon catheter isdeflated and withdrawn, leaving the stent deployed at the treatmentarea. A self expanding stent includes a material that has physicalproperties that do not require balloon expansion; however, a balloon canbe used. These stents are typically manufactured in their finalclinically relevant size and are temporarily reduced in size and mountedonto a delivery system; however, this is not required. The deploymentstrategy is similar to that of the balloon expandable stent except thata retaining system (e.g., sheath, adhesive, etc.) is withdrawn,degrades, breaks, etc. after the stent is positioned in the treatmentarea. After the retaining system is withdrawn, degrades or is broken,the stent expands. As can be appreciated, expansion of such a stent canbe facilitated by use of a balloon, heat, etc.; however, this is notrequired.

One or more surfaces of the stent can be treated so as to have generallysmooth surfaces. Generally, one or more ends of the stent are treated byfiling, buffing, polishing, grinding, coating, and/or the like to removeor reduce the number of rough and/or sharp surfaces; however, this isnot required. The smooth surfaces of the ends can be used to reducepotential damage to surrounding tissue as the stent is positioned inand/or expanded in a body passageway.

Referring now to FIGS. 3-14, there is illustrated a portion of the stentthat includes and/or is coated with one or more biological agents thatare used to improve the functionality and/or success of the medicaldevice such as, but not limited to inhibiting or preventing thrombosis.As can be appreciated, the coating combinations and structuralcombinations illustrated in FIGS. 3-14 can be used on the surgical graftas illustrated in FIG. 15, and/or on other medical devices. Asillustrated in FIGS. 3-15, the stent can include and/or be coated withone or more polymers and/or biological agents. The one or more polymerscan be porous or non-porous polymers. The one or more biological agentscan be, but are not limited to, anti-biotic agents, anti-body targetedtherapy agents, anti-hypertensive agents, anti-microbial agents,anti-mitotic agents, anti-oxidants, anti-polymerases agents,anti-proliferative agents, anti-secretory agents, anti-tumor agents,anti-viral agents, bioactive agents, chemotherapeutic agents, cellularcomponents, cytoskeletal inhibitors, drug, growth factors, growth factorantagonists, hormones, immunosuppressive agents, living cells,non-steroidal anti-inflammatory drugs, radioactive materials,radio-therapeutic agents, thrombolytic agents, vasodilator agents, etc.Non-limiting examples of biological agents that can be used on a stentfor use in the vascular system include, but are not limited to, avascular active agent that inhibits and/or prevents restenosis, vascularnarrowing and/or in-stent restenosis. Non-limiting examples of suchbiological agents include anti-platelet compounds and/or anticoagulantcompounds such as, but not limited to, warfarin (Coumadin) and/orderivatives, aspirin and/or derivatives, clopidogrel and/or derivatives,ticlopadine and/or derivatives, hirdun and/or derivatives, dipyridamoleand/or derivatives, trapidil and/or derivatives, and/or heparin and/orlow molecular weight heparin and/or derivatives. As can be appreciated,one or more other anti-thrombotic biological agents can be combined withthe stent such as, but not limited to, taxol, taxol derivatives,cytochalasin, cytochalasin derivatives, paclitaxel, paclitaxelderivatives, rapamycin, rapamycin derivatives, 5-Phenylmethimazole,5-Phenylmethimazole derivatives, GM-CSF, GM-CSF derivatives, orcombinations thereof. For example, the amount of biological agentdelivered to a certain region of a patient's body can be controlled by,but not limited to, one or more of the following: a) selecting the typeof biological agent to be used on and/or in the stent, b) selecting theamount of biological agent to be used on and/or in the stent, c)selecting the coating thickness of the biological agent to be used onthe stent, d) selecting the drug concentration of the biological agentto be used on and/or in the stent, e) selecting the solubility of thebiological agent to be used on and/or in the stent, f) selecting thelocation the biological agent that is to be coated and/or impregnated onand/in the stent, g) selecting the amount of surface area of the stentthat is coated and/or impregnated with the biological agent, h)selecting the location of the biological agent on the stent, I)selecting the size, shape, amount and/or location of the one or moresurface structures, micro-structures and/or internal structures of thestent that include and/or are integrated with the biological agent, j)selecting the type and/or amount of polymer to be mixed with thebiological agent, k) selecting the type, amount and/or coating thicknessof the polymer coating used to at least partially coat and/orencapsulate the biological agent, etc. As can be appreciated, the amountof one or more biological agent delivered to a region of the body can beat least partially controlled in other or additional ways.

One or more biological agents on and/or in the stent can be controllablyreleased and/or immediately released to optimize their effects in atreatment area and/or to compliment the function and success of thestent in a treatment area. The controlled release of one or morebiological agents from the stent can be accomplished by 1) controllingthe size and/or shape of the surface structures, micro-structures and/orinternal structures in the stent, and 2) combining and/or coating one ormore biological agents with one or more polymers. As can be appreciated,the controlled release of one or more polymers can be accomplished byother and/or additional arrangements. The one or more polymers can alsoor alternatively be used to assist in binding the one or more biologicalagents to the stent. The one or more polymers can be biodegradable orbiostable. The one or more polymers can be formulated to form a bondbetween one or more biological agents and the stent; however, this isnot required. The one or more polymers and one or more biological agentscan be mixed together prior to being applied to the stent; however, thisis not required. The one or more polymers can be used to control therelease of one or more biological agents by molecular diffusion and/orby one or more other mechanisms; however, this is not required. Thethickness of the one or more polymer layers can be about 0.5-25μ;however, other coating thickness can be used. When one or morebiological agents are controllably released from the stent, the timeperiod the one or more biological agents are released from the stent canvary. Generally, one or more biological agent are released from thestent over a period of at least several days after the stent is insertedin the body of a patient. As can be appreciated, the time frame that oneor more of the biological agents can be released from the stent can belonger or shorter. The one or more biological agents that are releasedfrom the stent can be controllably released and/or non-controllablyreleased. The time period for the release of two or more biologicalagents from the stent can be the same or different. The type of the oneor more biological agents used on the stent, the release rate of the oneor more biological agents from the stent, and/or the concentration ofthe one or more biological agents being released from the stent during acertain time period is typically selected to deliver one or morebiological agents to the area of treatment so as to increase the successof the stent (e.g., inhibit or prevent thrombosis, inhibit or preventrestenosis, vascular narrowing and/or in-stent restenosis after thestent has been implanted in a body passageway, etc.). The stent can bedesigned such that one or more biological agents are released from thestent for at least several minutes to at least several days after thestent is inserted in the body of a patient. As can be appreciated, thetime frame that one or more of the biological agents can be releasedfrom the stent can be varied. The stent can be designed such that one ormore biological agents are released from the stent so as to inhibit orprevent thrombosis after the stent has been implanted without the needfor aggressive anti-platelet and/or anti-coagulation therapy. In onenon-limiting design of stent, the stent releases one or more biologicalagents over a period of time after being inserted in the body so that nofurther anti-platelet and/or anti-coagulation therapy is required afterthe stent has been implanted. In another and/or alternative non-limitingdesign of stent, the stent releases one or more biological agents over aperiod of time after being inserted in the body so that no furtheranti-platelet and/or anti-coagulation therapy is required about one dayto two weeks after the stent has been implanted. In still another and/oralternative non-limiting design of stent, the stent releases one or morebiological agents over a period of time after being inserted in the bodyso that no further anti-platelet and/or anti-coagulation therapy isrequired about two weeks to one month after the stent has beenimplanted. The stent of the present invention can be used overcomes therequirement of past implanted stents to have the patient on aggressiveanti-platelet and/or anti-coagulation therapy for months after the stenthas been implanted in the patient.

When the one or more biological agents are used in combination with anon-porous polymer to controlled release of the one or more biologicalagents by molecular diffusion, the one or more polymers include, but arenot limited to, polyamide, parylene C, parylene N, parylene F,poly(ethylene oxide), poly(ethylene glycol), poly(propylene oxide),silicone based polymers, polymers of methane, tetrafluoroethylene ortetramethyldisiloxane, a polymer derived from photopolymerizeablemonomers and/or derivatives thereof. Such polymer can be coated on thestent by vapor deposition or plasma deposition; however, other oradditional coating techniques can be used. The thickness of the one ormore non-porous polymer layer, when applied by catalyst-free vapordeposition or plasma deposition is about 0.5-25μ; however, other coatingthicknesses can be used.

The surface of the base structure of the stent can be treated to enhancethe coating of the stent and/or to enhance the mechanicalcharacteristics of the stent; however, this is not required. Suchsurface treatment techniques include, but are not limited to, cleaning,buffing, smoothing, etching (chemical etching, plasma etching, etc.),etc. When an etching process is used, various gasses can be used forsuch a surface treatment process such as, but not limited to, carbondioxide, nitrogen, oxygen, Freon, helium, hydrogen, etc. The plasmaetching process can be used to clean the surface of the stent, changethe surface properties of the stent so as to affect the adhesionproperties, lubricity properties, etc. of the surface of the stent. Ascan be appreciated, other or additional surface treatment processes canbe used prior to the coating of one or more biological agents and/orpolymers on the surface of the stent.

As illustrated in FIGS. 3-6, various coating combinations can be used onthe stent. Referring to FIG. 3, the base structure 40 of the stentincludes a layer 50 of biological agent. The layer of biological agentcan include one or more biological agents. In one non-limiting example,the biological agent includes trapidil, trapidil derivatives, warfarin(Coumadin) and/or derivatives, aspirin and/or derivatives, clopidogreland/or derivatives, ticlopadine and/or derivatives, hirdun and/orderivatives, dipyridamole and/or derivatives, and/or heparin and/or lowmolecular weight heparin and/or derivatives. The one or more biologicalagents can also or alternatively include taxol, taxol derivatives,cytochalasin, cytochalasin derivatives, paclitaxel, paclitaxelderivatives, rapamycin, rapamycin derivatives, 5-Phenylmethimazole,5-Phenylmethimazole derivatives, GM-CSF, GM-CSF derivatives, orcombinations thereof. A polymer layer 60 is coated on the top of layer50. The polymer layer can include one or more polymers. The polymerlayer can include one or more porous polymers and/or non-porouspolymers, and/or one or more biostable and/or biodegradable polymers.Non-limiting examples of one or more polymers that can be used include,but are not limited to, parylene, parylene C, parylene N, parylene F,PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG, chitosan and/orderivatives of one or more of these polymers. In one non-limitingexample, the polymer layer includes one or more non-porous polymers toat least partially control a rate of release by molecular diffusion ofthe one or more biological agents of layer 50 from stent 20. The one ormore non-porous polymers can include, but is not limited to, parylene C,parylene N, parylene F and/or a parylene derivative.

As illustrated in FIG. 4, the base structure 40 of stent 20 includes alayer 70 of polymer and biological agent. Layer 70 can include one ormore biological agents mixed with one or more polymers. In onenon-limiting example, the biological agent includes trapidil, trapidilderivatives, warfarin (Coumadin) and/or derivatives, aspirin and/orderivatives, clopidogrel and/or derivatives, ticlopadine and/orderivatives, hirdun and/or derivatives, dipyridamole and/or derivatives,and/or heparin and/or low molecular weight heparin and/or derivatives.The one or more biological agents can also or alternatively includetaxol, taxol derivatives, cytochalasin, cytochalasin derivatives,paclitaxel, paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF, GM-CSFderivatives, or combinations thereof. The one or more polymers caninclude one or more porous and/or non-porous polymers, and/or one ormore biostable and/or biodegradable polymers. Non-limiting examples ofone or more polymers that can be used include, but are not limited to,parylene, parylene C, parylene N, parylene F, PLGA, PEVA, PLA, PBMA,POE, PGA, PLLA, PAA, PEG, chitosan and/or derivatives of one or more ofthese polymers. In one non-limiting example, the one or more polymersincluded in layer 70 include a non-porous polymer to at least partiallycontrol a rate of release by molecular diffusion of the one or morebiological agents in layer 70. The non-porous polymer can include, butis not limited to, parylene C, parylene N, parylene F and/or a parylenederivative.

As illustrated in FIG. 5, the base structure 40 of stent 20 includes alayer 80 of polymer. Layer 80 can include one or more porous polymersand/or non-porous polymers, and/or one or more biostable and/orbiodegradable polymers. Non-limiting examples of one or more polymersthat can be used include, but are not limited to, parylene, parylene C,parylene N, parylene F, PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG,chitosan and/or derivatives of one or more of these polymers. The one ormore non-porous polymers, when used, can include, but are not limitedto, parylene C, parylene N, parylene F and/or a parylene derivative. Alayer 90 of one or more biological agents is coated on top of polymerlayer 80. Polymer layer 8 can be used to facilitate in the securing oflayer 90 to the stent; however, this is not required. In onenon-limiting example, the biological agent includes trapidil, trapidilderivatives, warfarin (Coumadin) and/or derivatives, aspirin and/orderivatives, clopidogrel and/or derivatives, ticlopadine and/orderivatives, hirdun and/or derivatives, dipyridamole and/or derivatives,and/or heparin and/or low molecular weight heparin and/or derivatives.The one or more biological agents can also or alternatively includetaxol, taxol derivatives, cytochalasin, cytochalasin derivatives,paclitaxel, paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF, GM-CSFderivatives, or combinations thereof. The placement of a layer ofbiological agent on the top surface of the stent can provide a burst ofbiological agent in the treatment area (e.g., body passageway, etc.)after insertion of the stent. In one non-limiting example, the one ormore biological agents include trapidil and/or derivatives thereof.

As illustrated in FIG. 6, the base structure 40 of stent 20 includes alayer 100 of one or more biological agents. In one non-limiting example,the biological agent includes trapidil, trapidil derivatives, warfarin(Coumadin) and/or derivatives, aspirin and/or derivatives, clopidogreland/or derivatives, ticlopadine and/or derivatives, hirdun and/orderivatives, dipyridamole and/or derivatives, and/or heparin and/or lowmolecular weight heparin and/or derivatives. The one or more biologicalagents can also or alternatively include taxol, taxol derivatives,cytochalasin, cytochalasin derivatives, paclitaxel, paclitaxelderivatives, rapamycin, rapamycin derivatives, 5-Phenylmethimazole,5-Phenylmethimazole derivatives, GM-CSF, GM-CSF derivatives, orcombinations thereof. A polymer layer 110 is coated on the top of layer100. The polymer layer can include one or more polymers. The polymerlayer can include one or more porous polymers and/or non-porouspolymers, and/or one or more biostable and/or biodegradable polymers.Non-limiting examples of one or more polymers that can be used include,but are not limited to, parylene, parylene C, parylene N, parylene F,PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG, chitosan and/orderivatives of one or more of these polymers. In one non-limitingexample, the polymer layer includes one or more non-porous polymers toat least partially control a rate of release by molecular diffusion ofthe one or more biological agents of layer 100 from stent 20. The one ormore non-porous polymers can include, but are not limited to, paryleneC, parylene N, parylene F and/or a parylene derivative. A layer 120 ofbiological agent is coated on top of polymer layer 110. Layer 120 caninclude one or more biological agents. In one non-limiting example, thebiological agent includes trapidil, trapidil derivatives, warfarin(Coumadin) and/or derivatives, aspirin and/or derivatives, clopidogreland/or derivatives, ticlopadine and/or derivatives, hirdun and/orderivatives, dipyridamole and/or derivatives, and/or heparin and/or lowmolecular weight heparin and/or derivatives. The one or more biologicalagents can also or alternatively include taxol, taxol derivatives,cytochalasin, cytochalasin derivatives, paclitaxel, paclitaxelderivatives, rapamycin, rapamycin derivatives, 5-Phenylmethimazole,5-Phenylmethimazole derivatives, GM-CSF, GM-CSF derivatives, orcombinations thereof. The placement of a layer of biological agent onthe top surface of the stent provide can provide a burst of one or morebiological agents in the treatment area (e.g., body passageway, etc.)after insertion of the stent. In one non-limiting example, thebiological agent includes trapidil, trapidil derivatives, warfarin(Coumadin) and/or derivatives, aspirin and/or derivatives, clopidogreland/or derivatives, ticlopadine and/or derivatives, hirdun and/orderivatives, dipyridamole and/or derivatives, and/or heparin and/or lowmolecular weight heparin and/or derivatives. The one or more biologicalagents can also or alternatively include taxol, taxol derivatives,cytochalasin, cytochalasin derivatives, paclitaxel, paclitaxelderivatives, rapamycin, rapamycin derivatives, 5-Phenylmethimazole,5-Phenylmethimazole derivatives, GM-CSF, GM-CSF derivatives, orcombinations thereof. As can be appreciated, other combinations ofpolymer layer and layer of biological agent can be used on the stent.These other combinations are also encompassed within the scope of thepresent invention.

Referring now to FIG. 7, the base structure 40 of stent 20 includes oneor more surface structures and/or micro-structures 200. The one or moresurface structures and/or micro-structures can be formed in the basestructure during the formation of the base structure and/or from thetreatment of the base structure (e.g. etching, mechanical drill, lasercutting, water cutting, etc.) and/or from one or more micro-machiningprocesses. The one or more surface structures and/or micro-structures200 are shown to include one or more biological agents 210; however, itcan be appreciated that the one or more surface structures and/ormicro-structures 200 can include a combination of one or more polymersand one or more biological agents, or only one or more polymers. In onenon-limiting example, the biological agent includes trapidil, trapidilderivatives, warfarin (Coumadin) and/or derivatives, aspirin and/orderivatives, clopidogrel and/or derivatives, ticlopadine and/orderivatives, hirdun and/or derivatives, dipyridamole and/or derivatives,and/or heparin and/or low molecular weight heparin and/or derivatives.The one or more biological agents can also or alternatively includetaxol, taxol derivatives, cytochalasin, cytochalasin derivatives,paclitaxel, paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF, GM-CSFderivatives, or combinations thereof. The size of the one or moresurface structures and/or micro-structures can be used to at leastpartially control the rate of release of the one or more biologicalagents and/or polymers from the one or more surface structures and/ormicro-structures. A polymer layer 220 is coated on the top surface ofthe base structure 40. The polymer layer can include one or morepolymers. The polymer layer can include one or more porous polymersand/or non-porous polymers, and/or one or more biostable and/orbiodegradable polymers. Non-limiting examples of one or more polymersthat can be used include, but are not limited to, parylene, parylene C,parylene N, parylene F, PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG,chitosan and/or derivatives of one or more of these polymers. In onenon-limiting example, the polymer layer includes one or more non-porouspolymers to at least partially control a rate of release by moleculardiffusion of the one or more biological agents in the one or moresurface structures and/or micro-structures 200. The one or morenon-porous polymers can include, but are not limited to, parylene C,parylene N, parylene F and/or a parylene derivative.

Referring now to FIG. 8, the base structure 40 of stent 20 includes oneor more surface structures and/or micro-structures 250. The one or moresurface structures and/or micro-structures can be formed in the basestructure during the formation of the base structure and/or from thetreatment of the base structure (e.g. etching, mechanical drill, lasercutting, water cutting, etc.) and/or from one or more micro-machiningprocesses. The one or more surface structures and/or micro-structures250 are shown to include one or more biological agents 260; however, itcan be appreciated that the one or more surface structures and/ormicro-structures 250 can include a combination of one or more polymersand one or more biological agents, or only one or more polymers. In onenon-limiting example, the biological agent includes trapidil, trapidilderivatives, warfarin (Coumadin) and/or derivatives, aspirin and/orderivatives, clopidogrel and/or derivatives, ticlopadine and/orderivatives, hirdun and/or derivatives, dipyridamole and/or derivatives,and/or heparin and/or low molecular weight heparin and/or derivatives.The one or more biological agents can also or alternatively includetaxol, taxol derivatives, cytochalasin, cytochalasin derivatives,paclitaxel, paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF, GM-CSFderivatives, or combinations thereof. The size of the one or moresurface structures and/or micro-structures can be used to at leastpartially control the rate of release of the one or more biologicalagents and/or polymers from the one or more surface structures and/ormicro-structures. A layer 270 of biological agent is coated on the topsurface of the base structure. Layer 270 can include one or morebiological agents. In one non-limiting example, the biological agentincludes trapidil, trapidil derivatives, warfarin (Coumadin) and/orderivatives, aspirin and/or derivatives, clopidogrel and/or derivatives,ticlopadine and/or derivatives, hirdun and/or derivatives, dipyridamoleand/or derivatives, and/or heparin and/or low molecular weight heparinand/or derivatives. The one or more biological agents can also oralternatively include taxol, taxol derivatives, cytochalasin,cytochalasin derivatives, paclitaxel, paclitaxel derivatives, rapamycin,rapamycin derivatives, 5-Phenylmethimazole, 5-Phenylmethimazolederivatives, GM-CSF, GM-CSF derivatives, or combinations thereof. Theplacement of a layer of biological agent on the top surface of the stentcan provide a burst of one or more biological agent in the treatmentarea after insertion of the stent. In one non-limiting example, thebiological agent includes trapidil, trapidil derivatives, warfarin(Coumadin) and/or derivatives, aspirin and/or derivatives, clopidogreland/or derivatives, ticlopadine and/or derivatives, hirdun and/orderivatives, dipyridamole and/or derivatives, and/or heparin and/or lowmolecular weight heparin and/or derivatives. The one or more biologicalagents can also or alternatively include taxol, taxol derivatives,cytochalasin, cytochalasin derivatives, paclitaxel, paclitaxelderivatives, rapamycin, rapamycin derivatives, 5-Phenylmethimazole,5-Phenylmethimazole derivatives, GM-CSF, GM-CSF derivatives, orcombinations thereof. As can be appreciated, the one or more biologicalagents of layer 270 and in the one or more surface structures and/ormicro-structures 250 can be the same or different.

Referring now to FIG. 9, the base structure 40 of stent 20 includes oneor more surface structures and/or micro-structures 300. The one or moresurface structures and/or micro-structures can be formed in the basestructure during the formation of the base structure and/or from thetreatment of the base structure (e.g. etching, mechanical drill, lasercutting, water cutting, etc.) and/or from one or more micro-machiningprocesses. The one or more surface structures and/or micro-structures300 are shown to include one or more biological agents 310; however, itcan be appreciated that the one or more surface structures and/ormicro-structures 300 can include a combination of one or more polymersand one or more biological agents, or only one or more polymers. In onenon-limiting example, the biological agent includes trapidil, trapidilderivatives, warfarin (Coumadin) and/or derivatives, aspirin and/orderivatives, clopidogrel and/or derivatives, ticlopadine and/orderivatives, hirdun and/or derivatives, dipyridamole and/or derivatives,and/or heparin and/or low molecular weight heparin and/or derivatives.The one or more biological agents can also or alternatively includetaxol, taxol derivatives, cytochalasin, cytochalasin derivatives,paclitaxel, paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF, GM-CSFderivatives, or combinations thereof. The size of the one or moresurface structures and/or micro-structures can be used to at leastpartially control the rate of release of the one or more biologicalagents and/or polymers from the one or more surface structures and/ormicro-structures. A layer 320 of biological agent is coated on the topsurface of the base structure. Layer 320 can include one or morebiological agents. In one non-limitin, example, the biological agentincludes trapidil, trapidil derivatives, warfarin (Coumadin) and/orderivatives, aspirin and/or derivatives, clopidogrel and/or derivatives,ticlopadine and/or derivatives, hirdun and/or derivatives, dipyridamoleand/or derivatives, and/or heparin and/or low molecular weight heparinand/or derivatives. The one or more biological agents can also oralternatively include taxol, taxol derivatives, cytochalasin,cytochalasin derivatives, paclitaxel, paclitaxel derivatives, rapamycin,rapamycin derivatives, 5-Phenylmethimazole, 5-Phenylmethimazolederivatives, GM-CSF, GM-CSF derivatives, or combinations thereof. As canbe appreciated, the one or more biological agents of layer 320 and inthe one or more surface structures and/or micro-structures 300 can bethe same or different. A polymer layer 330 is coated on the top surfaceof the layer 310 of biological agent. The polymer layer can include oneor more polymers. The polymer layer can include one or more porouspolymers and/or non-porous polymers, and/or one or more biostable and/orbiodegradable polymers. Non-limiting examples of one or more polymersthat can be used include, but are not limited to, parylene, parylene C,parylene N, parylene F, PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG,chitosan and/or derivatives of one or more of these polymers. In onenon-limiting example, the polymer layer includes one or more non-porouspolymers to at least partially control a rate of release by moleculardiffusion of the one or more biological agents in the one or moresurface structures and/or micro-structures 300 and/or in layer 310. Theone or more non-porous polymers can include, but are not limited to,parylene C, parylene N, parylene F and/or a parylene derivative. As canbe appreciated, a layer that includes one or more biological agents, notshown, can be coated on layer 320 to provide a burst of one or morebiological agent in the treatment area after insertion of the stent. Ascan also be appreciated, other combinations of polymer layer and layerof biological agent can be used on the medical. These other combinationsare also encompassed within the scope of the present invention.

Referring now to FIG. 10, the base structure 40 of stent 20 includes oneor more needles or micro-needles 350. The one or more needles ormicro-needles are formed on the surface of the base structure. The oneor more needles or micro-needles are formed from one or more biologicalagents and/or one or more polymer 360. A layer 362 of biological agentand/or polymer is also formed on the surface of the base structure. Inone non-limiting example, the one or more needles or micro-needles 350are formed from one or more biological agents that include trapidil,trapidil derivatives, warfarin (Coumadin) and/or derivatives, aspirinand/or derivatives, clopidogrel and/or derivatives, ticlopadine and/orderivatives, hirdun and/or derivatives, dipyridamole and/or derivatives,and/or heparin and/or low molecular weight heparin and/or derivatives.The one or more biological agents can also or alternatively includetaxol, taxol derivatives, cytochalasin, cytochalasin derivatives,paclitaxel, paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF, GM-CSFderivatives, or combinations thereof. In this non-limiting example,layer 362 is also formed from one or more biological agents that includetrapidil, trapidil derivatives, warfarin (Coumadin) and/or derivatives,aspirin and/or derivatives, clopidogrel and/or derivatives, ticlopadineand/or derivatives, hirdun and/or derivatives, dipyridamole and/orderivatives, and/or heparin and/or low molecular weight heparin and/orderivatives. The one or more biological agents can also or alternativelyinclude taxol, taxol derivatives, cytochalasin, cytochalasinderivatives, paclitaxel, paclitaxel derivatives, rapamycin, rapamycinderivatives, 5-Phenylmethimazole, 5-Phenylmethimazole derivatives,GM-CSF, GM-CSF derivatives, or combinations thereof. As can beappreciated, the one or more biological agents in layer 362 and formingthe one or more needles or micro-needles 350 can be the same ordifferent. The use of one or more biological agents to coat the topsurface of the base structure and/or to form one or more needles ormicro-needles can provide a burst of one or more biological agent in thetreatment area (e.g., body passageway, etc.) after insertion of thestent. In another and/or alternative non-limiting example, the one ormore needles or micro-needles 350 are formed from one or more biologicalagents that include trapidil, trapidil derivatives, warfarin (Coumadin)and/or derivatives, aspirin and/or derivatives, clopidogrel and/orderivatives, ticlopadine and/or derivatives, hirdun and/or derivatives,dipyridamole and/or derivatives, and/or heparin and/or low molecularweight heparin and/or derivatives. The one or more biological agents canalso or alternatively include taxol, taxol derivatives, cytochalasin,cytochalasin derivatives, paclitaxel, paclitaxel derivatives, rapamycin,rapamycin derivatives, 5-Phenylmethimazole, 5-Phenylmethimazolederivatives, GM-CSF, GM-CSF derivatives, or combinations thereof. Inthis non-limiting example, layer 362 is formed from one or morepolymers. The polymer layer can include one or more polymers. Thepolymer layer can include one or more porous polymers and/or non-porouspolymers, and/or one or more biostable and/or biodegradable polymers.Non-limiting examples of one or more polymers that can be used include,but are not limited to, parylene, parylene C, parylene N, parylene F,PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG, chitosan and/orderivatives of one or more of these polymers. When the one or morepolymers are non-porous polymers, the one or more non-porous polymerscan include, but are not limited to, parylene C, parylene N, parylene Fand/or a parylene derivative. The use of one or more biological agentsto form one or more needles or micro-needles can provide a burst of oneor more biological agent in the treatment area (e.g., body passageway,etc.) after insertion of the stent. In still another and/or alternativenon-limiting example, the one or more needles or micro-needles 350 areformed from one or more polymers. The polymer layer can include one ormore polymers. The polymer layer can include one or more porous polymersand/or non-porous polymers, and/or one or more biostable and/orbiodegradable polymers. Non-limiting examples of one or more polymersthat can be used include, but are not limited to, parylene, parylene C,parylene N, parylene F, PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG,chitosan and/or derivatives of one or more of these polymers. When theone or more polymers are non-porous polymers, the one or more non-porouspolymers can include, but are not limited to, parylene C, parylene N,parylene F and/or a parylene derivative. In this non-limiting example,layer 362 is formed from one or more biological agents that includetrapidil, trapidil derivatives, warfarin (Coumadin) and/or derivatives,aspirin and/or derivatives, clopidogrel and/or derivatives, ticlopadineand/or derivatives, hirdun and/or derivatives, dipyridamole and/orderivatives, and/or heparin and/or low molecular weight heparin and/orderivatives. The one or more biological agents can also or alternativelyinclude taxol, taxol derivatives, cytochalasin, cytochalasinderivatives, paclitaxel, paclitaxel derivatives, rapamycin, rapamycinderivatives, 5-Phenylmethimazole, 5-Phenylmethimazole derivatives,GM-CSF, GM-CSF derivatives, or combinations thereof. The use of one ormore biological agents to form layer 362 can provide a burst of one ormore biological agent in the treatment area (e.g., body passageway,etc.) after insertion of the stent; however, this is not required.

Referring now to FIG. 11, the base structure 40 of stent 20 includes oneor more needles or micro-needles 400. The one or more needles ormicro-needles are formed on the surface of the base structure. The oneor more needles or micro-needles are formed from one or more biologicalagents and one or more polymers 410. A layer 412 of biological agentand/or polymer is also formed on the surface of the base structure. Ascan be appreciated, the composition of layer 412 and forming thecomposition of the one or more needles or micro-needles 400 can be thesame or different. In one non-limiting example, the one or morebiological agents that at least partially forms layer 412 and/or the oneor more needles or micro-needles 400 include trapidil, trapidilderivatives, warfarin (Coumadin) and/or derivatives, aspirin and/orderivatives, clopidogrel and/or derivatives, ticlopadine and/orderivatives, hirdun and/or derivatives, dipyridamole and/or derivatives,and/or heparin and/or low molecular weight heparin and/or derivatives.The one or more biological agents can also or alternatively includetaxol, taxol derivatives, cytochalasin, cytochalasin derivatives,paclitaxel, paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF, GM-CSFderivatives, or combinations thereof. The one or more polymers that atleast partially form layer 412 and/or the one or more needles ormicro-needles 400 can include one or more porous and/or non-porouspolymers, and/or one or more biostable and/or biodegradable polymers.Non-limiting examples of one or more polymers that can be used include,but are not limited to, parylene, parylene C, parylene N, parylene F,PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG, chitosan and/orderivatives of one or more of these polymers. In one non-limitingexample, the one or more polymers that at least partially form layer 412and/or the one or more needles or micro-needles 400 include a non-porouspolymer to at least partially control a rate of release by moleculardiffusion of the one or more biological agents that are mixed with thepolymer. The inclusion of one or more biological agents in the one ormore needles or micro-needles can provide controlled release ofbiological agent in the treatment area (e.g., body passageway, etc.)after insertion of the stent; however, this is not required. The use ofone or more biological agents to form layer 412 and/or one or moreneedles or micro-needles 400 can provide a burst of one or morebiological agent in the treatment area (e.g., body passageway, etc.)after insertion of the stent; however, this is not required.

Referring now to FIG. 12, FIG. 12 is a modification of the arrangementillustrated in FIG. 10. In FIG. 12, a coating 470, that is formed of oneor more polymers and/or biological agents is placed over one or moreneedles or micro-needles 450 and layer 462. Specifically, the basestructure 40 of stent 20 includes one or more needles or micro-needles450. The one or more needles or micro-needles are formed on the surfaceof the base structure. The one or more needles or micro-needles areformed from one or more biological agents and/or polymers 460. A layer462 of biological agent and/or polymer is also formed on the surface ofthe base structure. The composition of layer 462 and one or more needlesor micro-needles can be the same or different. In one non-limitingexample, the one or more biological agents that can at least partiallyform layer 463 and/or one or more needles or micro-needles 450 includetrapidil, trapidil derivatives, warfarin (Coumadin) and/or derivatives,aspirin and/or derivatives, clopidogrel and/or derivatives, ticlopadineand/or derivatives, hirdun and/or derivatives, dipyridamole and/orderivatives, and/or heparin and/or low molecular weight heparin and/orderivatives. The one or more biological agents can also or alternativelyinclude taxol, taxol derivatives, cytochalasin, cytochalasinderivatives, paclitaxel, paclitaxel derivatives, rapamycin, rapamycinderivatives, 5-Phenylmethimazole, 5-Phenylmethimazole derivatives,GM-CSF, GM-CSF derivatives, or combinations thereof. The one or morepolymers that can at least partially form layer 463 and/or one or moreneedles or micro-needles include one or more porous polymers and/ornon-porous polymers, and/or one or more biostable and/or biodegradablepolymers. Non-limiting examples of one or more polymers that can be usedinclude, but are not limited to, parylene, parylene C, parylene N,parylene F, PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG, chitosanand/or derivatives of one or more of these polymers. In one non-limitingexample, the one or more polymers that can at least partially form layer463 and/or one or more needles or micro-needles 450 include one or morenon-porous polymer such as, but not limited to, parylene C, parylene N,parylene F and/or a parylene derivative. The one or more non-porouspolymers can be used to at least partially control a rate of release bymolecular diffusion of the one or more biological agents in layer 463and/or in the one or more needles or micro-needles 450; however, this isnot required. Layer 470 that is coated on the top of the one or moreneedles or micro-needles and layer 462 includes one or more biologicalagents and/or polymers. In one non-limiting example, the one or morebiological agents that can at least partially form layer 470 includetrapidil, trapidil derivatives, warfarin (Coumadin) and/or derivatives,aspirin and/or derivatives, clopidogrel and/or derivatives, ticlopadineand/or derivatives, hirdun and/or derivatives, dipyridamole and/orderivatives, and/or heparin and/or low molecular weight heparin and/orderivatives. The one or more biological agents can also or alternativelyinclude taxol, taxol derivatives, cytochalasin, cytochalasinderivatives, paclitaxel, paclitaxel derivatives, rapamycin, rapamycinderivatives, 5-Phenylmethimazole, 5-Phenylmethimazole derivatives,GM-CSF, GM-CSF derivatives, or combinations thereof. In one non-limitingexample, the one or more polymers that can at least partially form layer470 include one or more porous and/or non-porous polymers, and/or one ormore biostable and/or biodegradable polymers. Non-limiting examples ofone or more polymers that can be used include, but are not limited to,parylene, parylene C, parylene N, parylene F, PLGA, PEVA, PLA, PBMA,POE, PGA, PLLA, PAA, PEG, chitosan and/or derivatives of one or more ofthese polymers. When the one or more polymers include one or morenon-porous polymers, such non-porous polymer can include, but is notlimited to, parylene C, parylene N, parylene F and/or a parylenederivative. The one or more non-porous polymers can be used to at leastpartially control a rate of release by molecular diffusion of the one ormore biological agents in layer 463, layer 470 and/or in the one or moreneedles or micro-needles 450; however, this is not required. When one ormore biological agents at least partially form layer 470 and/or arecoated on layer 470, not shown, the one or more biological agents canprovide a burst of one or more biological agent in the treatment area(e.g., body passageway, etc.) after insertion of the stent; however,this is not required.

Referring now to FIG. 13, FIG. 13 is a modification of the arrangementillustrated in FIG. 11. In FIG. 13, a coating 520, that is formed of oneor more polymers and/or biological agents is placed over one or moreneedles or micro-needles 500 and layer 512. The composition of layer 520and layer 512 and/or one or more needles or micro-needles can be thesame or different. Specifically, the base structure 40 of stent 20includes one or more needles or micro-needles 500. The one or moreneedles or micro-needles are formed on the surface of the basestructure. The one or more needles or micro-needles are formed from amixture of one or more biological agents and one or more polymers 510. Alayer 512 of biological agent and polymer is also formed on the surfaceof the base structure. As can be appreciated, layer 512 and/or one ormore needles or micro-needles 500 can be formed only of one or morepolymers or one or more biological agents. The composition of layer 512and one or more needles or micro-needles 500 can be the same ordifferent. In one non-limiting example, the one or more biologicalagents that can at least partially form layer 512 and/or one or moreneedles or micro-needles 500 include trapidil, trapidil derivatives,warfarin (Coumadin) and/or derivatives, aspirin and/or derivatives,clopidogrel and/or derivatives, ticlopadine and/or derivatives, hirdunand/or derivatives, dipyridamole and/or derivatives, and/or heparinand/or low molecular weight heparin and/or derivatives. The one or morebiological agents can also or alternatively include taxol, taxolderivatives, cytochalasin, cytochalasin derivatives, paclitaxel,paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF, GM-CSFderivatives, or combinations thereof. The one or more polymers that canat least partially form layer 512 and/or one or more needles ormicro-needles 500 include one or more porous polymers and/or non-porouspolymers, and/or one or more biostable and/or biodegradable polymers.Non-limiting examples of one or more polymers that can be used include,but are not limited to, parylene, parylene C, parylene N, parylene F,PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG, chitosan and/orderivatives of one or more of these polymers. In one non-limitingexample, the one or more polymers that can at least partially form layer512 and/or one or more needles or micro-needles 500 include one or morenon-porous polymers such as, but not limited to, parylene C, parylene N,parylene F and/or a parylene derivative. The one or more non-porouspolymers can be used to at least partially control a rate of release bymolecular diffusion of the one or more biological agents in layer 512and/or in the one or more needles or micro-needles 500; however, this isnot required. In one non-limiting example, the one or more polymers thatcan at least partially form layer 520 include one or more porous and/ornon-porous polymers, and/or one or more biostable and/or biodegradablepolymers. Non-limiting examples of one or more polymers that can be usedinclude, but are not limited to, parylene, parylene C, parylene N,parylene F, PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG, chitosanand/or derivatives of one or more of these polymers. When the one ormore polymers include one or more non-porous polymers, such non-porouspolymer can include, but not limited to, parylene C, parylene N,parylene F and/or a parylene derivative. The one or more non-porouspolymers can be used to at least partially control a rate of release bymolecular diffusion of the one or more biological agents in layer 512,layer 520 and/or in the one or more needles or micro-needles 500;however, this is not required. When one or more biological agents atleast partially forms layer 520 and/or are coated on layer 520, notshown, the one or more biological agents can provide a burst of one ormore biological agent in the treatment area (e.g., body passageway,etc.) after insertion of the stent; however, this is not required.

Referring now to FIG. 14, FIG. 14 is another modification of thearrangement illustrated in FIG. 11. In FIG. 14, one or more internalchannels 570 are formed in one or more needles or micro-needles 550. Theone or more internal channels 570 can include one or more biologicalagent and/or polymers. Specifically, the base structure 40 of stent 20includes one or more needles or micro-needles 550. The one or moreneedles or micro-needles are formed on the surface of the basestructure. The one or more needles or micro-needles are formed from oneor more polymers and/or biological agents 560. A layer 562 of polymerand/or biological agent is also formed on the surface of the basestructure. The composition of layer 562 and one or more needles ormicro-needles can be the same or different. The one or more polymersthat can at least partially form layer 562 and/or one or more needles ormicro-needles 550 include one or more porous polymers and/or non-porouspolymers, and/or one or more biostable and/or biodegradable polymers.Non-limiting examples of one or more polymers that can be used include,but are not limited to, parylene, parylene C, parylene N, parylene F,PLGA, PEVA, PLA, PBMA, POE, PGA, PLLA, PAA, PEG, chitosan and/orderivatives of one or more of these polymers. In one non-limitingexample, the one or more polymers that can at least partially form layer562 and/or one or more needles or micro-needles 550 include one or morenon-porous polymers such as, but not limited to, parylene C, parylene N,parylene F and/or a parylene derivative. The one or more non-porouspolymers can be used to at least partially control a rate of release bymolecular diffusion of the one or more biological agents in layer 562,in the one or more needles or micro-needles 550, and/or in one or moreinternal channels 570; however, this is not required. One or more of theneedles or micro-needles 550 include an internal channel 570. Theinternal channel is illustrated as including one or more biologicalagents 580; however, it can be appreciated that one or more channels caninclude a mixture of one or more polymers and/or biological agents, oronly one or more polymers. In one non-limiting example, the one or morebiological agents includes trapidil, trapidil derivatives, warfarin(Coumadin) and/or derivatives, aspirin and/or derivatives, clopidogreland/or derivatives, ticlopadine and/or derivatives, hirdun and/orderivatives, dipyridamole and/or derivatives, and/or heparin and/or lowmolecular weight heparin and/or derivatives. The one or more biologicalagents can also or alternatively include taxol, taxol derivatives,cytochalasin, cytochalasin derivatives, paclitaxel, paclitaxelderivatives, rapamycin, rapamycin derivatives, 5-Phenylmethimazole,5-Phenylmethimazole derivatives, GM-CSF, GM-CSF derivatives, orcombinations thereof. The top opening of the channel enables delivery ofone or more biological agents directly into treatment area (e.g., a wallof a body passageway or organ, etc.). The one or more biological agentsin internal channel 570 can pass through and/or molecularly diffusethrough the one or more polymers that at least partially form the one ormore needles or micro-needles; however, this is not required. Therelease of the one or more biological agents through the one or morepolymers that at least partially forms the one or more needles ormicro-needles can be a controlled or an uncontrolled release rate. Ascan be appreciated, a layer of biological agent, not shown, can becoated on one or more needles or micro-needles 550. The layer ofbiological agent could include one or more biological agents. Theplacement of the layer of biological agent on the one or more needles ormicro-needles 550 can provide a burst of one or more biological agentsin the treatment area; however, this is not required. As can beappreciated, other combinations of polymer layer and/or layer ofbiological agent can be used on the stent. As can also or alternativelybe appreciated, a layer of polymer, not shown, can be coated on one ormore needles or micro-needles 550. The layer of polymer could includeone or more polymers. The placement of the layer of polymer on the oneor more needles or micro-needles 550 can be used to a) at leastpartially control a release rate of one or more biological agents fromthe stent, and/or 2) provide structural support and/or protection to oneor more needles or micro-needles. As can be appreciated, the polymerlayer, when used, can have other or additional functions. These othercombinations are also encompassed within the scope of the presentinvention.

Referring now to FIG. 17, there is illustrated an enlarged portion of asurface of a stent 20 which includes a surface needle, micro-needle orother type of structure or micro-structure 700. The needle is shown toinclude at least one biological agent 710; however, the needle can alsoor alternatively include one or more polymers, adhesives, etc. Thestent, when in the form of a stent, is illustrated as being in anexpanded state. When the stent is inserted or expanded in a treatmentarea, the needle 700 on the outer surface of the stent engages and/or atleast partially penetrates into blood vessel or organ V. When the needleincludes one or more biological agents, the one or more biologicalagents are at least partially locally applied to a treatment area. Thiscan be a significant advantage over system wide treatment with one ormore biological agents. The local treatment with one or more biologicalagent via the needle can more effectively and/or efficiently direct thedesired agents to a treated area. The release of one or more biologicalagents from the needle can be controlled, if desired, to direct thedesired amount of one or more biological agents to a treated area over adesired period of time. When the stent is expanded in a blood vessel,the one or more needles enable local delivery of one or more biologicalagents into the wall of the blood vessel. This local delivery isespecially advantageous in large and/or thick blood vessels whereinsystem wide drug treatment is not very effective. In addition, the localdelivery of biological agent by the needle directly into the bloodvessel can be more effective than only releasing the biological agentfrom the surface of the stent since diffusion from the surface of thestent to the larger and/or thicker blood vessel may not be as effectiveas direct delivery by the needles to the blood vessel. The one or moreneedles on the stent surface can also or alternatively be used tofacilitate in securing the stent to the treatment area during theexpansion and/or insertion of the stent in a treatment area.

Referring now to FIG. 15, there is provided a surgical graft 600. Thesurgical graft is typically at least partially formed of a flexiblematerial. The material used to form the surgical graft is selected towithstand the manufacturing process that is needed to be accomplished inorder to produce the surgical graft. These manufacturing processes caninclude, but are not limited to, ion beam deposition or implantation,sputter coating, vacuum deposition and/or other coating processes. Onenon-limiting material is Gortex; however, other or additional materialscan be used (e.g., polyethylene tetraphthlate (Dacron), expandedpolytetrafluoroethylene (e.g., Gortex, Impra, etc.), etc. The surgicalgraft can be used in a variety of body passageways. One non-limiting useof the surgical graft is to graft to or replace a portion of a damagedblood vessel. The surgical graft 600 has a generally tubular shape;however, many other shapes can be used. As best illustrated in FIG. 16,the surgical graft includes a body portion 610. The inner surface 620 ofthe body portion includes a plurality of threads 630 extending from theinner surface 630 of the body portion. A layer 640 including one or morebiological agents and/or polymers is applied to the inner surface of thebody portion. As illustrated in FIG. 16, layer 640 only partiallyencapsulates threads 630; however, this is not required. It can beappreciated that layer 640 is applied in sufficient quantity to fullyencapsulate threads 630. In one non-limiting example, the one or morebiological agents in layer 640 include trapidil, trapidil derivatives,warfarin (Coumadin) and/or derivatives, aspirin and/or derivatives,clopidogrel and/or derivatives, ticlopadine and/or derivatives, hirdunand/or derivatives, dipyridamole and/or derivatives, and/or heparinand/or low molecular weight heparin and/or derivatives. The one or morebiological agents can also or alternatively include taxol, taxolderivatives, cytochalasin, cytochalasin derivatives, paclitaxel,paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF, GM-CSFderivatives, or combinations thereof. As can be appreciated, layer 640can include a combination of biological agent and polymer, or only apolymer. Referring again to FIG. 16, a layer 650 is coated on layer 640.Layer 650 can include one or more polymers. The layer can include one ormore porous and/or non-porous polymers and/or one or more biostableand/or biodegradable polymers. Non-limiting examples of one or morepolymers that can be used include, but are not limited to, parylene,parylene C, parylene N, parylene F, PLGA, PEVA, PLA, PBMA, POE, PGA,PLLA, PAA, PEG, chitosan and/or derivatives of one or more of thesepolymers. In one non-limiting example, the polymer layer includes one ormore non-porous polymers to at least partially control a rate of releaseby molecular diffusion of the one or more biological agents in layer 640and/or layer 650. The one or more non-porous polymers can include, butare not limited to, parylene C, parylene N, parylene F and/or a parylenederivative. Layer 650 is shown to only partially encapsulate threads630. As can be appreciated, sufficient amount of layer 650 can be usedto fully encapsulate thread 630. As can be appreciated, a layer ofbiological agent, not shown, can be coated on layer 650. The layer ofbiological agent could include one or more biological agents. Theplacement of the layer of biological agent on the top surface of layer650 can provide a burst of one or more biological agents in thetreatment area (e.g., body passageway, etc.) after insertion of thesurgical graft; however, this is not required. As can be appreciated,other combinations of polymer layer and layer of biological agent can beused on the surgical graft. Non-limiting examples of such combinationsare illustrated in FIGS. 3-14. These other combination are alsoencompassed within the scope of the present invention.

The following is a non-limiting example of the manufacture of a medicaldevice in the form of a stent in accordance with the present invention.A medical device structure in the form of a stent for use in a bodypassageway (e.g., vascular system, etc.) is selected. The base structureis formed of a durable, biostable metal material. As can be appreciated,the base structure can be made of a nonmetallic material and/or abiodegradable material. The surface of the base structure of the medicaldevice is plasma etched and/or cleaned. A porous or non-porous polymerlayer is applied to the etched surface of the base structure. One ormore biological agents are then applied to the surface of the polymerlayer. As can be appreciated, the one or more biological agents can beapplied to the surface of the stent prior to applying the porous ornon-porous polymer layer. At least one non-porous polymer layer isapplied over the one or more layers of biological agents so as to atleast partially control the rate of release of the one or morebiological agents by molecular diffusion through the non-porous polymerlayer. The one or more non-porous polymers can include, but are notlimited to, parylene C, parylene N, parylene F and/or a parylenederivative. A layer of biological agents can be applied over the finalnon-porous polymer layer for an additional fast release of thebiological agent; however, this is not required. The at least onenon-porous layer is applied via polymerization from a monomer vaporwhich is solvent or catalyst-free and is self curing. At least one layerof the biological agent can be deposited on the surface of the basestructure or polymer by a number of methods such as, but not limited to,dipping, rolling, brushing, spraying, particle atomization, sonicationor the like. Sonication can be used to deposit one or more biologicalagents and/or polymers on the surface of the base structure. Sonicationinvolves the application of ultrasonic waves to a stream of fluid thatmay or may not contain the biological agent and/or the polymer material.The fluid can include, but is not limited to, methanol, ethanol,isopropanol, acetone, water, saline, or any other organic or inorganicsolvent. The sonicated stream is broken into droplets of the fluid thatmay vary in size from less than 1 micron to several microns in diameteror more. The size of the droplets can be varied by controlling thefrequency of the sonicating device. The droplets can be applied to themedical device evenly or in various thickness configurations throughcontrolling the rotation of the medical device. The one or morebiological agents that are applied to the medical device can include,but are not limited to, trapidil, trapidil derivatives, warfarin(Coumadin) and/or derivatives, aspirin and/or derivatives, clopidogreland/or derivatives, ticlopadine and/or derivatives, hirdun and/orderivatives, dipyridamole and/or derivatives, and/or heparin and/or lowmolecular weight heparin and/or derivatives. The one or more biologicalagents can also or alternatively include taxol, taxol derivatives,cytochalasin, cytochalasin derivatives, paclitaxel, paclitaxelderivatives, rapamycin, rapamycin derivatives, 5-Phenylmethimazole,5-Phenylmethimazole derivatives, GM-CSF, GM-CSF derivatives, orcombinations thereof.

The medical device of the present invention can be used in conjunctionwith other biological agents. For instance, the success of the medicaldevice can be enhanced by infusing, injecting and/or consuming orallythe same and/or different biological agents that are being released fromthe medical device. The introduction of one or more biological agentsfrom a source other than the medical device can have an additive orsynergistic effect which can enhance the success of the medical device.Solid dosage forms of one or more biological agents for oraladministration can be used. Such solid forms can include, but are notlimited to, capsules, tablets, effervescent tablets, chewable tablets,pills, powders, sachets, granules and gels. In such solid dosage forms,the one or more biological agents can be admixed with at least onefiller material such as, but not limited to, sucrose, lactose or starch.Such dosage forms can also comprise, as in normal practice, additionalsubstances such as, but not limited to, inert diluents (e.g.,lubricating agents, etc.). When capsules, tablets, effervescent tabletsor pills are used, the dosage form can also include buffering agents.Soft gelatin capsules can be prepared to contain a mixture of thebiological agent in combination with vegetable oil or other types ofoil. Hard gelatin capsules can contain granules of the biological agentin combination with a solid carrier such as, but not limited to,lactose, potato starch, corn starch, cellulose derivatives of gelatin,etc. Tablets and pills can be prepared with enteric coatings foradditional time release characteristics. Liquid dosage forms of thebiological agent for oral administration can include pharmaceuticallyacceptable emulsions, solutions, suspensions, syrups, elixirs, etc.

It will thus be seen that the objects set forth above, among those madeapparent from the preceding description, are efficiently attained, andsince certain changes may be made in the constructions set forth withoutdeparting from the spirit and scope of the invention, it is intendedthat all matter contained in the above description and shown in theaccompanying drawings shall be interpreted as illustrative and not in alimiting sense. The invention has been described with reference topreferred and alternate embodiments. Modifications and alterations willbecome apparent to those skilled in the art upon reading andunderstanding the detailed discussion of the invention provided herein.This invention is intended to include all such modifications andalterations insofar as they come within the scope of the presentinvention. It is also to be understood that the following claims areintended to cover all of the generic and specific features of theinvention herein described and all statements of the scope of theinvention, which, as a matter of language, might be said to falltherebetween.

1. A method of treating a damaged vascular system of a patient with amedical device without having to use long term body-wide aggressiveanti-platelet and/or anti-coagulation therapy after the implantation ofthe medical device comprising: a) identifying a damaged region of thevascular system; b) opening a section or replacing a section of saiddamaged region of the vascular system by or with said medical device,said medical device being a stent or surgical graft, said medical deviceincluding a biological agent, said biological agent inhibiting orpreventing thrombosis; and, c) allowing said patient to recover from thesurgical procedure with no use or short term use of less than about twomonths of post operative body-wide anti-platelet and/or anti-coagulationtherapy.
 2. The method as defined in claim 1, wherein said short termuse is less than about forty days.
 3. The method as defined in claim 2,wherein said short term use is less than about one week.
 4. The methodas defined in claim 3, wherein said short term use is less than abouttwo days.
 5. The method as defined in claim 1, wherein said one or morebiological agents include trapidil, trapidil derivatives, warfarin,warfarin derivatives, aspirin, aspirin derivatives, clopidogrel,clopidogrel derivatives, ticlopadine, ticlopadine derivatives, hirdun,hirdun derivatives, dipyridamole, dipyridamole derivatives, heparin,heparin derivatives, or combinations thereof.
 6. The method as definedin claim 2, wherein said one or more biological agents include trapidil,trapidil derivatives, warfarin, warfarin derivatives, aspirin, aspirinderivatives, clopidogrel, clopidogrel derivatives, ticlopadine,ticlopadine derivatives, hirdun, hirdun derivatives, dipyridamole,dipyridamole derivatives, heparin, heparin derivatives, or combinationsthereof.
 7. The method as defined in claim 5, wherein said one or morebiological agents include trapidil, trapidil derivatives, orcombinations there.
 8. The method as defined in claim 6, wherein saidone or more biological agents include trapidil, trapidil derivatives, orcombinations there.
 9. The method as defined in claim 7, wherein saidone or more biological agents additionally include taxol, taxolderivatives, cytochalasin, cytochalasin derivatives, paclitaxel,paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF, GM-CSFderivatives, or combinations thereof.
 10. The method as defined in claim8, wherein said one or more biological agents additionally includetaxol, taxol derivatives, cytochalasin, cytochalasin derivatives,paclitaxel, paclitaxel derivatives, rapamycin, rapamycin derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF, GM-CSFderivatives, or combinations thereof.
 11. The method as defined in claim1, wherein said medical device includes at least one polymer layerhaving a coating thickness, a molecular weight, a molecular structure orcombinations thereof to at least partially controllably release at leastone of said biological agent, said polymer designed to release saidbiological agent from said medical device for at least about one dayafter said medical device is introduced into or on the body of apatient.
 12. The method as defined in claim 10, wherein said medicaldevice includes at least one polymer layer having a coating thickness, amolecular weight, a molecular structure or combinations thereof to atleast partially controllably release at least one of said biologicalagent, said polymer designed to release said biological agent from saidmedical device for at least about one day after said medical device isintroduced into or on the body of a patient.
 13. The method as definedin claim 11, wherein said polymer layer includes parylene, a parylenederivative, chitosan, a chitosan derivative, PLGA, a PLGA derivative,PLA, a PLA derivative, PEVA, a PEVA derivative, PBMA, a PBMA derivative,POE, POE derivative, PGA, PGA derivative, PLLA, PLLA derivative, PAA,PAA derivative, PEG, PEG derivative, or combinations thereof.
 14. Themethod as defined in claim 12, wherein said polymer layer includesparylene, a parylene derivative, chitosan, a chitosan derivative, PLGA,a PLGA derivative, PLA, a PLA derivative, PEVA, a PEVA derivative, PBMA,a PBMA derivative, POE, POE derivative, PGA, PGA derivative, PLLA, PLLAderivative, PAA, PAA derivative, PEG, PEG derivative, or combinationsthereof.
 15. The method as defined in claim 1, wherein said medicaldevice at least one micro-structure, surface structure or combinationsthereof.
 16. The method as defined in claim 14, wherein said medicaldevice at least one micro-structure, surface structure or combinationsthereof.
 17. The method as defined in claim 15, wherein said at leastone micro-structure, surface structure or combinations thereof includesa needle, a micro-needle or combinations thereof, and including the stepof expanding said medical device until said medical device at leastpartially engages an inner surface of a body passageway of said vascularsystem and cause said needle, a micro-needle or combinations thereof toat least partially penetrate into said body passageway.
 18. The methodas defined in claim 16, wherein said at least one micro-structure,surface structure or combinations thereof includes a needle, amicro-needle or combinations thereof, and including the step ofexpanding said medical device until said medical device at leastpartially engages an inner surface of a body passageway of said vascularsystem and cause said needle, a micro-needle or combinations thereof toat least partially penetrate into said body passageway.
 19. The methodas defined in claim 16, wherein said at least one micro-structure,surface structure or combinations thereof includes at least onebiological agent.
 20. The method as defined in claim 18, wherein said atleast one micro-structure, surface structure or combinations thereofincludes at least one biological agent.
 21. The method as defined inclaim 20, wherein said at least one biological agent included in said atleast one micro-structure, surface structure or combinations thereof atleast partially inhibits thrombosis.
 22. A method of treating a damagedvascular system of a patient with a medical device without having to uselong term body-wide aggressive anti-platelet and/or anti-coagulationtherapy after the implantation of the medical device comprising: a)identifying a damaged region of the vascular system; b) opening asection of said damaged region of the vascular system with use of saidmedical device, said medical device being a stent, said medical deviceincluding a biological agent, said biological agent including at leastone agent selected from the group consisting of warfarin, warfarinderivatives, aspirin, aspirin derivatives, clopidogrel, clopidogrelderivatives, ticlopadine, ticlopadine derivatives, hirdun, hirdunderivatives, dipyridamole, dipyridamole derivatives, trapidil, trapidilderivatives, 5-Phenylmethimazole, 5-Phenylmethimazole derivatives,GM-CSF, GM-CSF derivatives, heparin, heparin derivatives, low molecularweight heparin, low molecular weight heparin derivatives, orcombinations thereof. c) allowing said patient to recover from thesurgical procedure with no use or short term use of less than aboutforty days of post operative body-wide anti-platelet and/oranti-coagulation therapy.
 23. The method as defined in claim 22, whereinsaid biological agent includes trapidil, trapidil derivatives,5-Phenylmethimazole, 5-Phenylmethimazole derivatives, GM-CSF, GM-CSFderivatives.
 24. The method as defined in claim 23, wherein saidbiological agent includes two different biological agents.
 25. Themethod as defined in claim 24, wherein said biological agents includesat least two agents selected from the group consisting of trapidil,trapidil derivatives, taxol, taxol derivatives, cytochalasin,cytochalasin derivatives, paclitaxel, paclitaxel derivatives, rapamycin,rapamycin derivatives, 5-Phenylmethimazole, 5-Phenylmethimazolederivatives, GM-CSF, GM-CSF derivatives, or combinations thereof. 26.The method as defined in claim 22, wherein said medical device includesat least one polymer layer having a coating thickness, a molecularweight, a molecular structure or combinations thereof to at leastpartially controllably release at least one of said biological agent,said polymer designed to release said biological agent from said medicaldevice for at least about one day after said medical device isintroduced into or on the body of a patient.
 27. The method as definedin claim 25, wherein said medical device includes at least one polymerlayer having a coating thickness, a molecular weight, a molecularstructure or combinations thereof to at least partially controllablyrelease at least one of said biological agent, said polymer designed torelease said biological agent from said medical device for at leastabout one day after said medical device is introduced into or on thebody of a patient.
 28. The method as defined in claim 26, wherein saidpolymer layer includes parylene, parylene C; parylene F; parylene N,parylene derivative, parylene C derivative; parylene F derivative;parylene N derivative, or combinations thereof.
 29. The method asdefined in claim 27, wherein said polymer layer includes parylene,parylene C; parylene F; parylene N, parylene derivative, parylene Cderivative; parylene F derivative; parylene N derivative, orcombinations thereof.
 30. The method as defined in claim 22, whereinsaid medical device at least one micro-structure, said at least onemicro-structure includes a micro-needle, and including the step ofexpanding said medical device until said medical device at leastpartially engages an inner surface of a body passageway of said vascularsystem and cause said micro-needle to at least partially penetrate intosaid body passageway.
 31. The method as defined in claim 29, whereinsaid medical device at least one micro-structure, said at least onemicro-structure includes a micro-needle, and including the step ofexpanding said medical device until said medical device at leastpartially engages an inner surface of a body passageway of said vascularsystem and cause said micro-needle to at least partially penetrate intosaid body passageway.
 32. The method as defined in claim 30, whereinsaid at least one micro-structure includes at least one biologicalagent.
 33. The method as defined in claim 31, wherein said at least onemicro-structure includes at least one biological agent.